5-132334853-C-G

Variant names:

• chr5-132334853-C-G
• rs272879
• NM_003059.3:c.1182C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003059.3(SLC22A4):​c.1182C>G​(p.Thr394Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,612,414 control chromosomes in the GnomAD database, including 291,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27725 hom., cov: 31)
  • Exomes 𝑓: 0.59 (263432 hom.)
• Consequence: SLC22A4 NM_003059.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34
• Publications: 45 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-132334853-C-G is Benign according to our data. Variant chr5-132334853-C-G is described in ClinVar as Benign. ClinVar VariationId is 1285781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	NM_003059.3	MANE Select	c.1182C>G	p.Thr394Thr	synonymous	Exon 7 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.634G>C		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.1182C>G	p.Thr394Thr	synonymous	Exon 7 of 10	ENSP00000200652.3
	MIR3936HG	ENST00000621103.4	TSL:1	n.634G>C		non_coding_transcript_exon	Exon 6 of 8
	SLC22A4	ENST00000947750.1		c.1182C>G	p.Thr394Thr	synonymous	Exon 7 of 10	ENSP00000617809.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90741 AN: 151872 Hom.: 27696 Cov.: 31

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.565 AC: 142069 AN: 251374 AF XY: 0.552

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.598

Gnomad EAS exome AF: 0.358

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.611

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.595 AC: 868357 AN: 1460424 Hom.: 263432 Cov.: 40 AF XY: 0.587 AC XY: 426525 AN XY: 726606

African (AFR) AF: 0.660 AC: 22057 AN: 33440

American (AMR) AF: 0.676 AC: 30246 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 15656 AN: 26124

East Asian (EAS) AF: 0.333 AC: 13205 AN: 39668

South Asian (SAS) AF: 0.379 AC: 32693 AN: 86234

European-Finnish (FIN) AF: 0.494 AC: 26362 AN: 53408

Middle Eastern (MID) AF: 0.530 AC: 3054 AN: 5762

European-Non Finnish (NFE) AF: 0.621 AC: 689828 AN: 1110716

Other (OTH) AF: 0.584 AC: 35256 AN: 60352

GnomAD4 genome AF: 0.598 AC: 90823 AN: 151990 Hom.: 27725 Cov.: 31 AF XY: 0.587 AC XY: 43576 AN XY: 74274

African (AFR) AF: 0.655 AC: 27127 AN: 41432

American (AMR) AF: 0.650 AC: 9916 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2029 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1716 AN: 5174

South Asian (SAS) AF: 0.358 AC: 1727 AN: 4824

European-Finnish (FIN) AF: 0.488 AC: 5153 AN: 10550

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41019 AN: 67960

Other (OTH) AF: 0.610 AC: 1287 AN: 2110

Alfa AF: 0.602 Hom.: 8805

Bravo AF: 0.619

Asia WGS AF: 0.383 AC: 1335 AN: 3478

EpiCase AF: 0.614

EpiControl AF: 0.623

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.8
DANN	Benign	0.59
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs272879; hg19: chr5-131670546; COSMIC: COSV52358201;