rs757393385

Variant names:

• chr20-62666388-G-C
• rs757393385
• NM_016354.4:c.1285G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-62666388-G-C
• chr20-62666388-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016354.4(SLCO4A1):​c.1285G>C​(p.Val429Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLCO4A1 NM_016354.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.40

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-AS1 (HGNC:40537): (SLCO4A1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4A1	NM_016354.4	c.1285G>C	p.Val429Leu	missense_variant	Exon 7 of 12	ENST00000217159.6	NP_057438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4A1	ENST00000217159.6	c.1285G>C	p.Val429Leu	missense_variant	Exon 7 of 12	1	NM_016354.4	ENSP00000217159.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;.
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.24
Sift	Benign	0.64	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.41	B;B
Vest4		0.85
MutPred		0.58		Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);
MVP		0.53
MPC		0.81
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.35
gMVP		0.84

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

Other links and lift over

dbSNP: rs757393385; hg19: chr20-61297740;