2-218638390-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001379659.1(ZNF142):c.5613G>A(p.Glu1871=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,533,196 control chromosomes in the GnomAD database, including 1,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (344 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1239 hom.)
• Consequence: ZNF142 NM_001379659.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.467

Genes affected

ZNF142 (HGNC:12927): (zinc finger protein 142) The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 2-218638390-C-T is Benign according to our data. Variant chr2-218638390-C-T is described in ClinVar as [Benign]. Clinvar id is 1254978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.467 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF142	NM_001379659.1	c.5613G>A	p.Glu1871=	synonymous_variant	11/11	ENST00000411696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF142	ENST00000411696.7	c.5613G>A	p.Glu1871=	synonymous_variant	11/11	5	NM_001379659.1	P1
ZNF142	ENST00000449707.5	c.5013G>A	p.Glu1671=	synonymous_variant	10/10	1
ZNF142	ENST00000450765.5	c.*4838G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	1
ZNF142	ENST00000433921.5	c.*4838G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8580 AN: 152146 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0454 AC: 8621 AN: 189866 Hom.: 272 AF XY: 0.0440 AC XY: 4423 AN XY: 100558

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0348

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.0427

Gnomad FIN exome AF: 0.0308

Gnomad NFE exome AF: 0.0340

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0377 AC: 52103 AN: 1380932 Hom.: 1239 Cov.: 31 AF XY: 0.0378 AC XY: 25603 AN XY: 676780

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0330

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0424

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0424

GnomAD4 genome AF: 0.0564 AC: 8595 AN: 152264 Hom.: 344 Cov.: 32 AF XY: 0.0553 AC XY: 4118 AN XY: 74448

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0450 Hom.: 128

Bravo AF: 0.0592

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

ZNF142-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 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	-0.61
Cadd	Benign	5.8
Dann	Benign	0.76

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: rs1803383; hg19: chr2-219503113; COSMIC: COSV68742921; COSMIC: COSV68742921;