Variant 4-146293940-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001029998.6(SLC10A7):c.711A>G(p.Ile237Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,611,692 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 198 hom. )

Consequence

SLC10A7
NM_001029998.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.20

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026927292).

BP6

Variant 4-146293940-T-C is Benign according to our data. Variant chr4-146293940-T-C is described in ClinVar as [Benign]. Clinvar id is 1549029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6 linkuse as main transcript	c.711A>G	p.Ile237Met	missense_variant	8/12	ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000335472.12 linkuse as main transcript	c.711A>G	p.Ile237Met	missense_variant	8/12	1	NM_001029998.6	P1	Q0GE19-2

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

846

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0644

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.0164

AC:

4090

AN:

249500

Hom.:

170

AF XY:

0.0133

AC XY:

1791

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.0736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0792

Gnomad SAS exome

AF:

0.00165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.00759

GnomAD4 exome

AF:

0.00383

AC:

5586

AN:

1459440

Hom.:

198

Cov.:

AF XY:

0.00340

AC XY:

2471

AN XY:

725876

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0656

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0538

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00558

AC:

849

AN:

152252

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0646

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00267

Hom.:

Bravo

AF:

0.00906

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0136

AC:

1648

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SLC10A7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.21

DANN

Benign

0.68

DEOGEN2

Benign

0.022

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.1

.;L;L

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.91

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.22

T;T;T

Sift4G

Uncertain

0.022

D;T;T

Polyphen

0.0060

B;P;.

Vest4

0.17

MPC

0.42

ClinPred

0.011

GERP RS

-12

Varity_R

0.13

gMVP

0.71

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