chr6-160122098-G-T

Position:

• chr6-160122098-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003057.3(SLC22A1):​c.163G>T​(p.Val55Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39915586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.163G>T	p.Val55Leu	missense_variant	1/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.163G>T	p.Val55Leu	missense_variant	1/10
SLC22A1	XM_005267103.3	c.163G>T	p.Val55Leu	missense_variant	1/12
SLC22A1	XM_006715552.3	c.163G>T	p.Val55Leu	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.163G>T	p.Val55Leu	missense_variant	1/11	1	NM_003057.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2021

The c.163G>T (p.V55L) alteration is located in exon 1 (coding exon 1) of the SLC22A1 gene. This alteration results from a G to T substitution at nucleotide position 163, causing the valine (V) at amino acid position 55 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	.;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.7	L;L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;.;N;N
REVEL	Benign	0.17
Sift	Benign	0.082	T;.;D;D
Sift4G	Benign	0.15	T;.;D;D
Polyphen		0.75	P;P;D;.
Vest4		0.096
MutPred		0.41		Loss of glycosylation at S52 (P = 0.1141);Loss of glycosylation at S52 (P = 0.1141);Loss of glycosylation at S52 (P = 0.1141);Loss of glycosylation at S52 (P = 0.1141);
MVP		0.45
MPC		0.23
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.22
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-160543130;