Variant 4-146256917-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000507030.5(SLC10A7):c.1013G>T(p.Gly338Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLC10A7
ENST00000507030.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

SLC10A7 (HGNC:23088): (solute carrier family 10 member 7) Enables bile acid transmembrane transporter activity. Involved in several processes, including cellular calcium ion homeostasis; glycoprotein transport; and heparin biosynthetic process. Located in Golgi apparatus and endoplasmic reticulum. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC10A7 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=0.03915593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6 linkuse as main transcript	c.994-397G>T		intron_variant		ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000507030.5 linkuse as main transcript	c.1013G>T	p.Gly338Val	missense_variant	12/13	1			Q0GE19-1
SLC10A7	ENST00000335472.12 linkuse as main transcript	c.994-397G>T		intron_variant		1	NM_001029998.6	P1	Q0GE19-2
SLC10A7	ENST00000432059.6 linkuse as main transcript	c.955-397G>T		intron_variant		1			Q0GE19-3
SLC10A7	ENST00000693222.1 linkuse as main transcript	c.1084-397G>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000722

AC:

AN:

138542

Hom.:

AF XY:

0.0000134

AC XY:

AN XY:

74876

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1383934

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2022

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 338 of the SLC10A7 protein (p.Gly338Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with SLC10A7-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.44

DANN

Benign

0.29

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.34

M_CAP

Benign

0.0020

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

0.41

REVEL

Benign

0.0050

Sift

Benign

0.19

Sift4G

Benign

0.17

Vest4

0.064

MutPred

0.29

Loss of disorder (P = 0.0542);

MVP

0.067

ClinPred

0.033

GERP RS

-6.0

gMVP

0.58

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