Variant chr20-62658692-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016354.4(SLCO4A1):c.812C>A(p.Ala271Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,458,866 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: 0.0000055 ( 0 hom. )

Consequence

SLCO4A1
NM_016354.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO4A1	NM_016354.4 linkuse as main transcript	c.812C>A	p.Ala271Glu	missense_variant	3/12	ENST00000217159.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO4A1	ENST00000217159.6 linkuse as main transcript	c.812C>A	p.Ala271Glu	missense_variant	3/12	1	NM_016354.4	P1	Q96BD0-1
SLCO4A1	ENST00000370507.5 linkuse as main transcript	c.812C>A	p.Ala271Glu	missense_variant	2/11	1		P1	Q96BD0-1
SLCO4A1	ENST00000497209.5 linkuse as main transcript	c.812C>A	p.Ala271Glu	missense_variant, NMD_transcript_variant	3/10	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458866

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 27, 2022

The c.812C>A (p.A271E) alteration is located in exon 3 (coding exon 2) of the SLCO4A1 gene. This alteration results from a C to A substitution at nucleotide position 812, causing the alanine (A) at amino acid position 271 to be replaced by a glutamic acid (E). 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

0.89

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;.

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Pathogenic

3.1

M;M

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.010

D;D

Sift4G

Benign

0.095

T;T

Polyphen

0.99

D;D

Vest4

0.94

MutPred

0.68

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.73

MPC

0.88

ClinPred

0.97

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over