NM_016354.4:c.1285G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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]

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

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.1285G>C	p.Val429Leu	missense	Exon 7 of 12	NP_057438.3
	SLCO4A1-AS1	NR_024470.1		n.234C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO4A1	ENST00000217159.6	TSL:1 MANE Select	c.1285G>C	p.Val429Leu	missense	Exon 7 of 12	ENSP00000217159.1	Q96BD0-1
	SLCO4A1	ENST00000370507.5	TSL:1	c.1285G>C	p.Val429Leu	missense	Exon 6 of 11	ENSP00000359538.1	Q96BD0-1
	SLCO4A1-AS1	ENST00000433126.1	TSL:1	n.235C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		9.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.24
Sift	Benign	0.64	T
Sift4G	Benign	0.30	T
Polyphen		0.41	B
Vest4		0.85
MutPred		0.58		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
Mutation Taster		=53/46	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: rs757393385; hg19: chr20-61297740;