6-160348269-C-T

Variant names:

• chr6-160348269-C-T
• rs59711975
• NM_021977.4:c.-151C>T

Variant summary

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

The NM_021977.4(SLC22A3):​c.-151C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 785,310 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: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: SLC22A3 NM_021977.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 0 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [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=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.-151C>T		upstream_gene_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.-151C>T		upstream_gene_variant		1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000255 AC: 2 AN: 785310 Hom.: 0 Cov.: 11 AF XY: 0.00000266 AC XY: 1 AN XY: 375476

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16372

American (AMR) AF: 0.00 AC: 0 AN: 6732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10916

East Asian (EAS) AF: 0.00 AC: 0 AN: 21192

South Asian (SAS) AF: 0.00 AC: 0 AN: 14450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2244

European-Non Finnish (NFE) AF: 0.00000302 AC: 2 AN: 661252

Other (OTH) AF: 0.00 AC: 0 AN: 32282

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		-0.32
PromoterAI		-0.040	Neutral

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: rs59711975; hg19: chr6-160769301;