NM_003059.3:c.653-93G>C

Variant names:

• chr5-132322091-G-C
• rs3761659
• NM_003059.3:c.653-93G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003059.3(SLC22A4):​c.653-93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,146,206 control chromosomes in the GnomAD database, including 4,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (571 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4218 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-132322091-G-C is Benign according to our data. Variant chr5-132322091-G-C is described in ClinVar as Benign. ClinVar VariationId is 1280672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.653-93G>C		intron_variant	Intron 3 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.653-93G>C		intron_variant	Intron 3 of 9	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.825-9838C>G		intron_variant	Intron 7 of 7	1
MIR3936HG	ENST00000669845.1	n.451-9838C>G		intron_variant	Intron 3 of 3
SLC22A4	ENST00000425923.1	n.-93G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11668 AN: 151998 Hom.: 574 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.0795 AC: 79023 AN: 994090 Hom.: 4218 AF XY: 0.0786 AC XY: 40433 AN XY: 514522

African (AFR) AF: 0.0592 AC: 1439 AN: 24292

American (AMR) AF: 0.0340 AC: 1473 AN: 43342

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2498 AN: 22776

East Asian (EAS) AF: 0.292 AC: 10520 AN: 36012

South Asian (SAS) AF: 0.0522 AC: 3983 AN: 76242

European-Finnish (FIN) AF: 0.0755 AC: 3735 AN: 49468

Middle Eastern (MID) AF: 0.0626 AC: 200 AN: 3194

European-Non Finnish (NFE) AF: 0.0743 AC: 51608 AN: 694690

Other (OTH) AF: 0.0809 AC: 3567 AN: 44074

GnomAD4 genome AF: 0.0767 AC: 11668 AN: 152116 Hom.: 571 Cov.: 32 AF XY: 0.0758 AC XY: 5634 AN XY: 74366

African (AFR) AF: 0.0616 AC: 2554 AN: 41476

American (AMR) AF: 0.0493 AC: 754 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1388 AN: 5172

South Asian (SAS) AF: 0.0646 AC: 311 AN: 4816

European-Finnish (FIN) AF: 0.0752 AC: 796 AN: 10584

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5211 AN: 67996

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0785 Hom.: 79

Bravo AF: 0.0746

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.48
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs3761659; hg19: chr5-131657784; COSMIC: COSV52360887; COSMIC: COSV52360887;