20-62656852-G-C

Variant names:

• chr20-62656852-G-C
• rs534641240
• NM_016354.4:c.398G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016354.4(SLCO4A1):​c.398G>C​(p.Arg133Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R133H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLCO4A1 NM_016354.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52
• Publications: 1 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016354.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO4A1	NM_016354.4	MANE Select	c.398G>C	p.Arg133Pro	missense	Exon 2 of 12	NP_057438.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO4A1	ENST00000217159.6	TSL:1 MANE Select	c.398G>C	p.Arg133Pro	missense	Exon 2 of 12	ENSP00000217159.1	Q96BD0-1
	SLCO4A1	ENST00000370507.5	TSL:1	c.398G>C	p.Arg133Pro	missense	Exon 1 of 11	ENSP00000359538.1	Q96BD0-1
	SLCO4A1	ENST00000497209.5	TSL:1	n.398G>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000434245.1	E1P5H9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.098	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		5.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.80	P
Vest4		0.76
MutPred		0.90		Loss of stability (P = 0.1383)
MVP		0.76
MPC		1.0
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		-0.0096	Neutral
Varity_R		0.91
gMVP		0.97
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs534641240; hg19: chr20-61288204;