rs12777

Variant names:

• chr5-132335969-C-G
• rs12777
• NM_003059.3:c.1413C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003059.3(SLC22A4):​c.1413C>G​(p.Gly471Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,614,026 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (79 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1193 hom.)
• Consequence: SLC22A4 NM_003059.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.311
• Publications: 16 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 5-132335969-C-G is Benign according to our data. Variant chr5-132335969-C-G is described in ClinVar as Benign. ClinVar VariationId is 805281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.311 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.1413C>G	p.Gly471Gly	synonymous_variant	Exon 8 of 10	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.1413C>G	p.Gly471Gly	synonymous_variant	Exon 8 of 10	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.561-1043G>C		intron_variant	Intron 5 of 7	1
MIR3936HG	ENST00000616965.1	n.344-1043G>C		intron_variant	Intron 3 of 4	5
MIR3936HG	ENST00000669845.1	n.187-1043G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4258 AN: 152184 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0388

GnomAD2 exomes AF: 0.0305 AC: 7672 AN: 251390 AF XY: 0.0312

Gnomad AFR exome AF: 0.00677

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0414

Gnomad OTH exome AF: 0.0478

GnomAD4 exome AF: 0.0372 AC: 54351 AN: 1461724 Hom.: 1193 Cov.: 32 AF XY: 0.0372 AC XY: 27043 AN XY: 727166

African (AFR) AF: 0.00965 AC: 323 AN: 33480

American (AMR) AF: 0.0270 AC: 1208 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 1605 AN: 26134

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39692

South Asian (SAS) AF: 0.0160 AC: 1378 AN: 86254

European-Finnish (FIN) AF: 0.0248 AC: 1327 AN: 53420

Middle Eastern (MID) AF: 0.119 AC: 688 AN: 5762

European-Non Finnish (NFE) AF: 0.0409 AC: 45525 AN: 1111874

Other (OTH) AF: 0.0379 AC: 2289 AN: 60386

GnomAD4 genome AF: 0.0279 AC: 4256 AN: 152302 Hom.: 79 Cov.: 32 AF XY: 0.0275 AC XY: 2046 AN XY: 74478

African (AFR) AF: 0.00729 AC: 303 AN: 41558

American (AMR) AF: 0.0325 AC: 497 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4828

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10614

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2714 AN: 68026

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.0408 Hom.: 119

Bravo AF: 0.0276

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.0467

EpiControl AF: 0.0461

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 27, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.9
DANN	Benign	0.70
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12777; hg19: chr5-131671662;