rs11568503

Variant names:

• chr5-132327296-C-A
• rs11568503
• NM_003059.3:c.844C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132327296-C-A
• chr5-132327296-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003059.3(SLC22A4):​c.844C>A​(p.Arg282Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000138 in 1,450,156 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: 0.0000014 (0 hom.)
• Consequence: SLC22A4 NM_003059.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• Publications: 0 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) 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. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.844C>A	p.Arg282Arg	synonymous_variant	Exon 5 of 10	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.844C>A	p.Arg282Arg	synonymous_variant	Exon 5 of 10	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.824+4893G>T		intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000425923.1	n.374C>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
MIR3936HG	ENST00000669845.1	n.450+4893G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450156 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 721560

⚠️ 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: 33180

American (AMR) AF: 0.00 AC: 0 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39430

South Asian (SAS) AF: 0.00 AC: 0 AN: 85392

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103134

Other (OTH) AF: 0.00 AC: 0 AN: 59892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), 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	-0.14
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.59		Position offset: 2

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

Other links and lift over

dbSNP: rs11568503; hg19: chr5-131662989;