20-62656690-C-G

Variant names:

• chr20-62656690-C-G
• rs200514917
• NM_016354.4:c.236C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016354.4(SLCO4A1):​c.236C>G​(p.Ser79Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign 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. S79L) 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: 2.90
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.236C>G	p.Ser79Trp	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.236C>G	p.Ser79Trp	missense	Exon 2 of 12	ENSP00000217159.1	Q96BD0-1
	SLCO4A1	ENST00000370507.5	TSL:1	c.236C>G	p.Ser79Trp	missense	Exon 1 of 11	ENSP00000359538.1	Q96BD0-1
	SLCO4A1	ENST00000497209.5	TSL:1	n.236C>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000434245.1	E1P5H9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.51		Loss of sheet (P = 0.0043)
MVP		0.75
MPC		0.92
ClinPred		0.98	D
GERP RS		3.8
PromoterAI		0.032	Neutral
Varity_R		0.27
gMVP		0.71
Mutation Taster		=85/15	polymorphism

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: rs200514917; hg19: chr20-61288042;