Variant 20-62657239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016354.4(SLCO4A1):c.785C>T(p.Pro262Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SLCO4A1
NM_016354.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO4A1	NM_016354.4 linkuse as main transcript	c.785C>T	p.Pro262Leu	missense_variant	2/12	ENST00000217159.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO4A1	ENST00000217159.6 linkuse as main transcript	c.785C>T	p.Pro262Leu	missense_variant	2/12	1	NM_016354.4	P1	Q96BD0-1
SLCO4A1	ENST00000370507.5 linkuse as main transcript	c.785C>T	p.Pro262Leu	missense_variant	1/11	1		P1	Q96BD0-1
SLCO4A1	ENST00000497209.5 linkuse as main transcript	c.785C>T	p.Pro262Leu	missense_variant, NMD_transcript_variant	2/10	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1378334

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676088

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:

9.39e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000108

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

Sep 27, 2021

The c.785C>T (p.P262L) alteration is located in exon 2 (coding exon 1) of the SLCO4A1 gene. This alteration results from a C to T substitution at nucleotide position 785, causing the proline (P) at amino acid position 262 to be replaced by a leucine (L). 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

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;.

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

0.21

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.70

Sift

Benign

0.047

D;D

Sift4G

Benign

0.089

T;T

Polyphen

0.99

D;D

Vest4

0.97

MutPred

0.85

Loss of methylation at K257 (P = 0.0806);Loss of methylation at K257 (P = 0.0806);

MVP

0.86

MPC

0.83

ClinPred

0.99

GERP RS

4.3

Varity_R

0.28

gMVP

0.88

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