rs77010315

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_181776.3(SLC36A2):c.260G>T(p.Gly87Val) variant causes a missense change. The variant allele was found at a frequency of 0.0105 in 1,613,846 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G87S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0086 ( 14 hom., cov: 32)

Exomes 𝑓: 0.011 ( 105 hom. )

Consequence

SLC36A2
NM_181776.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4O:2

Conservation

PhyloP100: 7.18

Publications

14 publications found

Variant links:

Genes affected

SLC36A2 (HGNC:18762): (solute carrier family 36 member 2) This gene encodes a pH-dependent proton-coupled amino acid transporter that belongs to the amino acid auxin permease 1 protein family. The encoded protein primarily transports small amino acids such as glycine, alanine and proline. Mutations in this gene are associated with iminoglycinuria and hyperglycinuria. [provided by RefSeq, Sep 2010]

SLC36A2 Gene-Disease associations (from GenCC):

iminoglycinuria
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
hyperglycinuria
Inheritance: AD, SD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SLC36A2 links:

ENSG00000297368 (HGNC:):

ENSG00000297368 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012553453).

BP6

Variant 5-151343594-C-A is Benign according to our data. Variant chr5-151343594-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2384.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS2

High Homozygotes in GnomAd4 at 14 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A2	NM_181776.3 link	c.260G>T	p.Gly87Val	missense_variant	Exon 3 of 10	ENST00000335244.9	NP_861441.2	Q495M3-1
SLC36A2	XM_005268377.5 link	c.260G>T	p.Gly87Val	missense_variant	Exon 3 of 10		XP_005268434.1
SLC36A2	XM_017009083.3 link	c.260G>T	p.Gly87Val	missense_variant	Exon 3 of 8		XP_016864572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC36A2	ENST00000335244.9 link	c.260G>T	p.Gly87Val	missense_variant	Exon 3 of 10	1	NM_181776.3	ENSP00000334223.4		Q495M3-1

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

1309

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00734

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00548

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00935

AC:

2350

AN:

251320

AF XY:

0.00976

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00524

Gnomad ASJ exome

AF:

0.0410

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00522

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0107

AC:

15676

AN:

1461736

Hom.:

105

Cov.:

AF XY:

0.0108

AC XY:

7856

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

33478

American (AMR)

AF:

0.00521

AC:

233

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0439

AC:

1148

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00385

AC:

332

AN:

86254

European-Finnish (FIN)

AF:

0.00502

AC:

268

AN:

53414

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0116

AC:

12860

AN:

1111892

Other (OTH)

AF:

0.0117

AC:

708

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

718

1436

2155

2873

3591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00859

AC:

1306

AN:

152110

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

660

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00227

AC:

AN:

41496

American (AMR)

AF:

0.00733

AC:

112

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00333

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00548

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

878

AN:

67990

Other (OTH)

AF:

0.00569

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00827

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0129

AC:

111

ExAC

AF:

0.00881

AC:

1070

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0161

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4Other:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hyperglycinuria

Uncertain:1Benign:1Other:1

May 28, 2019

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2008

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:curation

NM_181776.2:c.260G>T in the SLC36A2 gene has an allele frequency of 0.041 in Ashkenazi Jewish subpopulation in the gnomAD database, including 24 homozygous occurrences. Broer et al. reported this variant in a patient with iminoglycinuria . However, iminoglycinuria was only observed when homozygous SLC36A2 G87V was combined with SLC6A20 T199M (PMID: 19033659). Pathogenic computational verdict because pathogenic predictions from DANN, EIGEN, FATHMM-MKL, MutationAssessor, MutationTaster, PrimateAI and SIFT. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1; BS2; PP3. -

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC36A2: BS1, BS2 -

Nov 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Iminoglycinuria

Other:1

Dec 01, 2008

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Pathogenic

4.1

H;.

PhyloP100

7.2

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-8.2

D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.99

MVP

0.39

MPC

0.67

ClinPred

0.11

GERP RS

4.5

Varity_R

0.97

gMVP

0.72

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs77010315

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over