chr6-160121967-T-C

Variant names:

• chr6-160121967-T-C
• rs749926302
• NM_003057.3:c.32T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003057.3(SLC22A1):​c.32T>C​(p.Val11Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000189 in 1,613,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20429954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.32T>C	p.Val11Ala	missense_variant	Exon 1 of 11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.32T>C	p.Val11Ala	missense_variant	Exon 1 of 10		NP_694857.1
SLC22A1	XM_005267103.3	c.32T>C	p.Val11Ala	missense_variant	Exon 1 of 12		XP_005267160.1
SLC22A1	XM_006715552.3	c.32T>C	p.Val11Ala	missense_variant	Exon 1 of 9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.32T>C	p.Val11Ala	missense_variant	Exon 1 of 11	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000104 AC: 26 AN: 250792 Hom.: 0 AF XY: 0.000148 AC XY: 20 AN XY: 135506

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000196 AC: 286 AN: 1460908 Hom.: 0 Cov.: 30 AF XY: 0.000189 AC XY: 137 AN XY: 726636

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74346

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.0000494 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32T>C (p.V11A) alteration is located in exon 1 (coding exon 1) of the SLC22A1 gene. This alteration results from a T to C substitution at nucleotide position 32, causing the valine (V) at amino acid position 11 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.59
DEOGEN2	Benign	0.089	T;T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.75	.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.78	N;.;N;N
REVEL	Benign	0.24
Sift	Benign	0.71	T;.;T;T
Sift4G	Benign	0.53	T;.;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.058
MVP		0.58
MPC		0.16
ClinPred		0.046	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs749926302; hg19: chr6-160542999;