Variant 20-62657094-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016354.4(SLCO4A1):c.640G>A(p.Ala214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,598,226 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00049 ( 4 hom. )

Consequence

SLCO4A1
NM_016354.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.568

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:

SLCO4A1 (HGNC:):

SLCO4A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037004054).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO4A1	NM_016354.4 linkuse as main transcript	c.640G>A	p.Ala214Thr	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 linkuse as main transcript	c.640G>A	p.Ala214Thr	missense_variant	2/12	1	NM_016354.4	ENSP00000217159.1	Q96BD0-1
SLCO4A1	ENST00000370507.5 linkuse as main transcript	c.640G>A	p.Ala214Thr	missense_variant	1/11	1		ENSP00000359538.1	Q96BD0-1
SLCO4A1	ENST00000497209.5 linkuse as main transcript	n.640G>A		non_coding_transcript_exon_variant	2/10	1		ENSP00000434245.1	E1P5H9

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000818

AC:

180

AN:

220164

Hom.:

AF XY:

0.000630

AC XY:

AN XY:

120582

show subpopulations

Gnomad AFR exome

AF:

0.000144

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00642

Gnomad EAS exome

AF:

0.0000612

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000550

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.000492

AC:

711

AN:

1445888

Hom.:

Cov.:

AF XY:

0.000479

AC XY:

344

AN XY:

718802

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00598

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000316

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000479

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000714

Hom.:

Bravo

AF:

0.000582

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000589

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.640G>A (p.A214T) alteration is located in exon 2 (coding exon 1) of the SLCO4A1 gene. This alteration results from a G to A substitution at nucleotide position 640, causing the alanine (A) at amino acid position 214 to be replaced by a threonine (T). 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

0.062

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.14

DANN

Benign

0.62

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.36

T;.

M_CAP

Benign

0.0080

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.27

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.0090

Sift

Benign

0.92

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0020

B;B

Vest4

0.034

MVP

0.20

MPC

0.21

ClinPred

0.0037

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.34

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