Variant 4-146292972-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001029998.6(SLC10A7):c.730A>G(p.Ile244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,430,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SLC10A7
NM_001029998.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0780

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10478076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6 linkuse as main transcript	c.730A>G	p.Ile244Val	missense_variant	9/12	ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000335472.12 linkuse as main transcript	c.730A>G	p.Ile244Val	missense_variant	9/12	1	NM_001029998.6	P1	Q0GE19-2
SLC10A7	ENST00000507030.5 linkuse as main transcript	c.730A>G	p.Ile244Val	missense_variant	9/13	1			Q0GE19-1
SLC10A7	ENST00000432059.6 linkuse as main transcript	c.691A>G	p.Ile231Val	missense_variant	8/11	1			Q0GE19-3
SLC10A7	ENST00000693222.1 linkuse as main transcript	c.820A>G	p.Ile274Val	missense_variant	10/13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

243988

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132064

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000350

AC:

AN:

1430580

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713104

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:

0.00000459

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.730A>G (p.I244V) alteration is located in exon 9 (coding exon 9) of the SLC10A7 gene. This alteration results from a A to G substitution at nucleotide position 730, causing the isoleucine (I) at amino acid position 244 to be replaced by a valine (V). 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

0.077

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L

MutationTaster

Benign

0.91

D;D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.15

MVP

0.076

MPC

0.34

ClinPred

0.12

GERP RS

3.0

Varity_R

0.028

gMVP

0.33

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