11-93148617-T-C

Variant summary

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

The NM_152313.4(SLC36A4):c.1435A>G(p.Thr479Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC36A4
NM_152313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.351

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=0.05299896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC36A4	NM_152313.4 linkuse as main transcript	c.1435A>G	p.Thr479Ala	missense_variant	11/11	ENST00000326402.9
SLC36A4	NM_001286139.2 linkuse as main transcript	c.1030A>G	p.Thr344Ala	missense_variant	11/11
SLC36A4	XM_047426350.1 linkuse as main transcript	c.1378A>G	p.Thr460Ala	missense_variant	11/11
SLC36A4	XM_047426351.1 linkuse as main transcript	c.1117A>G	p.Thr373Ala	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC36A4	ENST00000326402.9 linkuse as main transcript	c.1435A>G	p.Thr479Ala	missense_variant	11/11	1	NM_152313.4	P1	Q6YBV0-1
SLC36A4	ENST00000529184.5 linkuse as main transcript	c.1030A>G	p.Thr344Ala	missense_variant	11/11	2			Q6YBV0-2
SLC36A4	ENST00000527503.1 linkuse as main transcript	n.1609A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460530

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

Asia WGS

AF:

0.00144

AC:

AN:

3478

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

Sep 01, 2021

The c.1435A>G (p.T479A) alteration is located in exon 11 (coding exon 11) of the SLC36A4 gene. This alteration results from a A to G substitution at nucleotide position 1435, causing the threonine (T) at amino acid position 479 to be replaced by an alanine (A). 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

Benign

0.058

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.19

Dann

Benign

0.68

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.045

Sift

Benign

0.30

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0

B;.

Vest4

0.045

MutPred

0.45

Loss of glycosylation at T479 (P = 0.0364);.;

MVP

0.014

MPC

0.041

ClinPred

0.11

GERP RS

-2.5

Varity_R

0.020

gMVP

0.62

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