11-93148580-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152313.4(SLC36A4):c.1472T>C(p.Phe491Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,459,878 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC36A4
NM_152313.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.774

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044214457).

BP6

Variant 11-93148580-A-G is Benign according to our data. Variant chr11-93148580-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2482127.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC36A4	NM_152313.4 linkuse as main transcript	c.1472T>C	p.Phe491Ser	missense_variant	11/11	ENST00000326402.9
SLC36A4	NM_001286139.2 linkuse as main transcript	c.1067T>C	p.Phe356Ser	missense_variant	11/11
SLC36A4	XM_047426350.1 linkuse as main transcript	c.1415T>C	p.Phe472Ser	missense_variant	11/11
SLC36A4	XM_047426351.1 linkuse as main transcript	c.1154T>C	p.Phe385Ser	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC36A4	ENST00000326402.9 linkuse as main transcript	c.1472T>C	p.Phe491Ser	missense_variant	11/11	1	NM_152313.4	P1	Q6YBV0-1
SLC36A4	ENST00000529184.5 linkuse as main transcript	c.1067T>C	p.Phe356Ser	missense_variant	11/11	2			Q6YBV0-2
SLC36A4	ENST00000527503.1 linkuse as main transcript	n.1646T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249786

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1459878

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

Cadd

Benign

7.3

Dann

Benign

0.75

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.043

Sift

Benign

0.54

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0

B;.

Vest4

0.037

MutPred

0.48

Gain of disorder (P = 2e-04);.;

MVP

0.030

MPC

0.062

ClinPred

0.0091

GERP RS

0.094

Varity_R

0.046

gMVP

0.49

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