20-62664951-T-C

Variant names:

• chr20-62664951-T-C
• NM_016354.4:c.1139T>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.1139T>C​(p.Leu380Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLCO4A1 NM_016354.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48
• 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]

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

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, 0.974

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.1139T>C	p.Leu380Pro	missense	Exon 6 of 12	NP_057438.3
	SLCO4A1-AS1	NR_024470.1		n.935A>G		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO4A1	ENST00000217159.6	TSL:1 MANE Select	c.1139T>C	p.Leu380Pro	missense	Exon 6 of 12	ENSP00000217159.1	Q96BD0-1
	SLCO4A1	ENST00000370507.5	TSL:1	c.1139T>C	p.Leu380Pro	missense	Exon 5 of 11	ENSP00000359538.1	Q96BD0-1
	SLCO4A1-AS1	ENST00000433126.1	TSL:1	n.936A>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.82		Loss of stability (P = 0.0323)
MVP		0.87
MPC		1.0
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.93
gMVP		0.95
Mutation Taster		=1/99	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

hg19: chr20-61296303;