11-93148839-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152313.4(SLC36A4):c.1213G>A(p.Gly405Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,597,728 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SLC36A4
NM_152313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.573

Variant links:

Genes affected

SLC36A4 (HGNC:19660): (solute carrier family 36 member 4) SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).[supplied by OMIM, Feb 2011]

SLC36A4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0330894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC36A4	NM_152313.4 linkuse as main transcript	c.1213G>A	p.Gly405Arg	missense_variant	11/11	ENST00000326402.9
SLC36A4	NM_001286139.2 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	11/11
SLC36A4	XM_047426350.1 linkuse as main transcript	c.1156G>A	p.Gly386Arg	missense_variant	11/11
SLC36A4	XM_047426351.1 linkuse as main transcript	c.895G>A	p.Gly299Arg	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC36A4	ENST00000326402.9 linkuse as main transcript	c.1213G>A	p.Gly405Arg	missense_variant	11/11	1	NM_152313.4	P1	Q6YBV0-1
SLC36A4	ENST00000529184.5 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	11/11	2			Q6YBV0-2
SLC36A4	ENST00000527503.1 linkuse as main transcript	n.1387G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

235332

Hom.:

AF XY:

0.000196

AC XY:

AN XY:

127574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

160

AN:

1445658

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

113

AN XY:

718810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000542

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.1213G>A (p.G405R) alteration is located in exon 11 (coding exon 11) of the SLC36A4 gene. This alteration results from a G to A substitution at nucleotide position 1213, causing the glycine (G) at amino acid position 405 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.47

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0080

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.064

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.20

Sift

Benign

0.20

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.52

P;.

Vest4

0.39

MutPred

0.88

Gain of methylation at G405 (P = 0.0169);.;

MVP

0.17

MPC

0.047

ClinPred

0.067

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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