Variant 3-196216719-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_152672.6(SLC51A):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,574,370 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

SLC51A
NM_152672.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

SLC51A (HGNC:29955): (solute carrier family 51 member A) Predicted to enable protein heterodimerization activity; protein homodimerization activity; and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. Implicated in progressive familial intrahepatic cholestasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC51A links:

LOC105374304 (HGNC:):

LOC105374304 links:

PCYT1A (HGNC:8754): (phosphate cytidylyltransferase 1A, choline) This gene belongs to the cytidylyltransferase family and is involved in the regulation of phosphatidylcholine biosynthesis. Mutations in this gene are associated with spondylometaphyseal dysplasia with cone-rod dystrophy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

PCYT1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0053415).

BP6

Variant 3-196216719-C-T is Benign according to our data. Variant chr3-196216719-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3034741.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC51A	NM_152672.6 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/9	ENST00000296327.10	NP_689885.4
LOC105374304	XR_001740544.2 linkuse as main transcript	n.1130+1945G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/9	1	NM_152672.6	ENSP00000296327	P1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000516

AC:

AN:

184154

Hom.:

AF XY:

0.000531

AC XY:

AN XY:

99772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000927

Gnomad ASJ exome

AF:

0.00364

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000402

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.000329

AC:

468

AN:

1422064

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

234

AN XY:

703872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00361

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000246

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000252

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.000309

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000451

Hom.:

Bravo

AF:

0.000442

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC51A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 27, 2022

This variant is classified as likely 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

0.081

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0088

.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;M

MutationTaster

Benign

0.70

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-7.7

D;N

REVEL

Benign

0.069

Sift

Benign

0.26

.;T

Sift4G

Benign

0.37

.;T

Polyphen

0.0030

.;B

Vest4

0.15

MVP

0.30

MPC

0.14

ClinPred

0.034

GERP RS

4.3

Varity_R

0.073

gMVP

0.50

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