5-151316858-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_181776.3(SLC36A2):c.1411G>A(p.Asp471Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,613,586 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00066 ( 8 hom. )

Consequence

SLC36A2
NM_181776.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.126

Publications

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

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005772382).

BP6

Variant 5-151316858-C-T is Benign according to our data. Variant chr5-151316858-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 788353.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00066 (965/1461616) while in subpopulation MID AF = 0.0189 (109/5762). AF 95% confidence interval is 0.016. There are 8 homozygotes in GnomAdExome4. There are 468 alleles in the male GnomAdExome4 subpopulation. Median coverage is 45. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 8 AR,AD,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A2	NM_181776.3	MANE Select	c.1411G>A	p.Asp471Asn	missense	Exon 10 of 10	NP_861441.2	Q495M3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC36A2	ENST00000335244.9	TSL:1 MANE Select	c.1411G>A	p.Asp471Asn	missense	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
SLC36A2	ENST00000518280.5	TSL:1	n.*882G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
SLC36A2	ENST00000518617.5	TSL:1	n.*979G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes

AF:

0.000731

AC:

111

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000994

AC:

250

AN:

251484

AF XY:

0.000986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000580

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000660

AC:

965

AN:

1461616

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

468

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33476

American (AMR)

AF:

0.000783

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

333

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000383

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5762

European-Non Finnish (NFE)

AF:

0.000296

AC:

329

AN:

1111838

Other (OTH)

AF:

0.00174

AC:

105

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000730

AC:

111

AN:

151970

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41458

American (AMR)

AF:

0.00118

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

67986

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000910

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000857

AC:

104

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00136

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

SLC36A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.89

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.00063

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.34

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.17

PhyloP100

-0.13

PrimateAI

Benign

0.26

PROVEAN

Benign

0.41

REVEL

Benign

0.045

Sift

Benign

0.82

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.032

MVP

0.048

MPC

0.13

ClinPred

0.012

GERP RS

-3.5

Varity_R

0.027

gMVP

0.19

Mutation Taster

=97/3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over