chr17-21415696-G-C

Position:

• chr17-21415696-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_021012.5(KCNJ12):​c.354G>C​(p.Arg118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (0 hom., cov: 51)
  • Exomes 𝑓: 0.48 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ12 NM_021012.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

Genes affected

KCNJ12 (HGNC:6258): (potassium inwardly rectifying channel subfamily J member 12) This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 17-21415696-G-C is Benign according to our data. Variant chr17-21415696-G-C is described in ClinVar as [Benign]. Clinvar id is 3060394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ12	NM_021012.5	c.354G>C	p.Arg118=	synonymous_variant	3/3	ENST00000583088.6
KCNJ12	XM_005256625.6	c.354G>C	p.Arg118=	synonymous_variant	3/3
KCNJ12	XM_011523831.3	c.354G>C	p.Arg118=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ12	ENST00000583088.6	c.354G>C	p.Arg118=	synonymous_variant	3/3	1	NM_021012.5	P1
KCNJ12	ENST00000331718.5	c.354G>C	p.Arg118=	synonymous_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 72036 AN: 144518 Hom.: 0 Cov.: 51 FAILED QC

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.498

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.478 AC: 329454 AN: 688648 Hom.: 0 Cov.: 185 AF XY: 0.477 AC XY: 169168 AN XY: 354550

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.498 AC: 72087 AN: 144620 Hom.: 0 Cov.: 51 AF XY: 0.498 AC XY: 35100 AN XY: 70444

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.498

Alfa AF: 0.499 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KCNJ12-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1657741; hg19: chr17-21319008; COSMIC: COSV59163596;