Variant 20-62657095-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016354.4(SLCO4A1):c.641C>T(p.Ala214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,597,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SLCO4A1
NM_016354.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.317

Variant links:

Genes affected

SLCO4A1 (HGNC:10953): (solute carrier organic anion transporter family member 4A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity and thyroid hormone transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO4A1 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=0.034335792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO4A1	NM_016354.4 link	c.641C>T	p.Ala214Val	missense_variant	2/12	ENST00000217159.6	NP_057438.3	Q96BD0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLCO4A1	ENST00000217159.6 link	c.641C>T	p.Ala214Val	missense_variant	2/12	1	NM_016354.4	ENSP00000217159.1	Q96BD0-1
SLCO4A1	ENST00000370507.5 link	c.641C>T	p.Ala214Val	missense_variant	1/11	1		ENSP00000359538.1	Q96BD0-1
SLCO4A1	ENST00000497209.5 link	n.641C>T		non_coding_transcript_exon_variant	2/10	1		ENSP00000434245.1	E1P5H9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

220060

Hom.:

AF XY:

0.0000581

AC XY:

AN XY:

120464

show subpopulations

Gnomad AFR exome

AF:

0.0000720

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000619

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000387

AC:

AN:

1445752

Hom.:

Cov.:

AF XY:

0.0000431

AC XY:

AN XY:

718698

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000466

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.0000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000498

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.050

DANN

Benign

0.63

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.38

T;.

M_CAP

Benign

0.0051

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.027

Sift

Benign

0.52

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

B;B

Vest4

0.045

MVP

0.20

MPC

0.22

ClinPred

0.018

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.35

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