20-62658692-C-A

Position:

• chr20-62658692-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

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]

ACMG classification

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	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	c.812C>A	p.Ala271Glu	missense_variant	3/12	1	NM_016354.4	P1
SLCO4A1	ENST00000370507.5	c.812C>A	p.Ala271Glu	missense_variant	2/11	1		P1
SLCO4A1	ENST00000497209.5	c.812C>A	p.Ala271Glu	missense_variant, NMD_transcript_variant	3/10	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1458866 Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5 AN XY: 725548

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.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.66	T
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	D
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.

Other links and lift over

hg19: chr20-61290044;