rs11568503

chr5-132327296-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_003059.3(SLC22A4):c.844C>T(p.Arg282Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000281 in 1,602,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SLC22A4 NM_003059.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_003059.3 Downstream stopcodon found after 625 codons.
• PP5: Variant 5-132327296-C-T is Pathogenic according to our data. Variant chr5-132327296-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A4	NM_003059.3	c.844C>T	p.Arg282Ter	stop_gained	5/10	ENST00000200652.4
MIR3936HG	NR_110997.1	n.824+4893G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A4	ENST00000200652.4	c.844C>T	p.Arg282Ter	stop_gained	5/10	1	NM_003059.3	P1
MIR3936HG	ENST00000621103.4	n.824+4893G>A		intron_variant, non_coding_transcript_variant		1
SLC22A4	ENST00000425923.1	n.374C>T		non_coding_transcript_exon_variant	3/3	3
MIR3936HG	ENST00000669845.1	n.450+4893G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000329 AC: 8 AN: 243456 Hom.: 0 AF XY: 0.0000379 AC XY: 5 AN XY: 131764

Gnomad AFR exome AF: 0.000447

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000920

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1450154 Hom.: 0 Cov.: 27 AF XY: 0.0000166 AC XY: 12 AN XY: 721560

Gnomad4 AFR exome AF: 0.000392

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000635

Gnomad4 OTH exome AF: 0.0000334

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152300 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74458

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000286 Hom.: 0

Bravo AF: 0.000193

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.65
Cadd	Pathogenic	42
Dann	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.97	D
MutationTaster	Benign	1.0	A
Vest4		0.95
GERP RS		5.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11568503; hg19: chr5-131662989; COSMIC: COSV99569170; COSMIC: COSV99569170;