rs77010315

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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).

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:3O:2

Conservation

PhyloP100: 7.18

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAd4 at 14 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

GnomAD3 exomes

AF:

0.00935

AC:

2350

AN:

251320

Hom.:

AF XY:

0.00976

AC XY:

1325

AN XY:

135812

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 SAS exome

AF:

0.00405

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

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00521

Gnomad4 ASJ exome

AF:

0.0439

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00385

Gnomad4 FIN exome

AF:

0.00502

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00859

AC:

1306

AN:

152110

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

660

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00227

Gnomad4 AMR

AF:

0.00733

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.00548

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.0126

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:3Other:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hyperglycinuria

Uncertain:1Benign:1Other:1

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. -

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

- -

not provided

Benign:2

Nov 01, 2022

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

- -

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over