4-146503857-C-T

Position:

• chr4-146503857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The ENST00000511374.5(SLC10A7):​c.251G>A​(p.Trp84Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC10A7 ENST00000511374.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0271 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-146503857-C-T is Pathogenic according to our data. Variant chr4-146503857-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 623256.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A7	NM_001029998.6	c.388G>A	p.Gly130Arg	missense_variant	4/12	ENST00000335472.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A7	ENST00000335472.12	c.388G>A	p.Gly130Arg	missense_variant	4/12	1	NM_001029998.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	.;D;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D;D;D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Uncertain	0.00010	D
MutationAssessor	Pathogenic	3.5	M;M;M;M
MutationTaster	Benign	1.0	A;D;D;D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-7.3	D;D;D;D
REVEL	Pathogenic	0.96
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.85
MutPred		0.90		Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);
MVP		0.38
MPC		1.4
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.82
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs1560973467; hg19: chr4-147425009;