NM_003057.3:c.516-99C>A

Variant names:

• chr6-160132133-C-A
• rs3737088
• NM_003057.3:c.516-99C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003057.3(SLC22A1):​c.516-99C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000181 in 1,106,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-99C>A		intron_variant	Intron 2 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-99C>A		intron_variant	Intron 2 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.516-99C>A		intron_variant	Intron 2 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.516-99C>A		intron_variant	Intron 2 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.516-99C>A		intron_variant	Intron 2 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000181 AC: 2 AN: 1106582 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 549500

African (AFR) AF: 0.00 AC: 0 AN: 24992

American (AMR) AF: 0.00 AC: 0 AN: 28070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18252

East Asian (EAS) AF: 0.00 AC: 0 AN: 34318

South Asian (SAS) AF: 0.00 AC: 0 AN: 60828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4726

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840274

Other (OTH) AF: 0.00 AC: 0 AN: 47402

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.015
DANN	Benign	0.58
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3737088; hg19: chr6-160553165;