chr6-160122053-G-T

Variant names:

• chr6-160122053-G-T
• rs753772607
• NM_003057.3:c.118G>T

Variant summary

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

The NM_003057.3(SLC22A1):​c.118G>T​(p.Val40Phe) variant causes a missense change involving the alteration of a non-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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V40I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 1 publications found

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

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_003057.3. 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
	SLC22A1	NM_003057.3	MANE Select	c.118G>T	p.Val40Phe	missense	Exon 1 of 11	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.118G>T	p.Val40Phe	missense	Exon 1 of 10	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.118G>T	p.Val40Phe	missense	Exon 1 of 9	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.118G>T	p.Val40Phe	missense	Exon 1 of 11	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.118G>T	p.Val40Phe	missense	Exon 1 of 12	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.118G>T	p.Val40Phe	missense	Exon 1 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.021	D
Polyphen		0.76	P
Vest4		0.48
MutPred		0.44		Loss of stability (P = 0.1955)
MVP		0.70
MPC		0.31
ClinPred		0.98	D
GERP RS		4.6
PromoterAI		-0.016	Neutral
Varity_R		0.50
gMVP		0.82
Mutation Taster		=69/31	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: rs753772607; hg19: chr6-160543085; COSMIC: COSV61451768;