2-218655682-C-T

Variant names:

• chr2-218655682-C-T
• rs3931102
• NM_001379659.1:c.280+468G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379659.1(ZNF142):​c.280+468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,930 control chromosomes in the GnomAD database, including 20,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20491 hom., cov: 31)
• Consequence: ZNF142 NM_001379659.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 10 publications found

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]

ZNF142 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with impaired speech and hyperkinetic movements

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF142	NM_001379659.1	c.280+468G>A		intron_variant	Intron 4 of 10	ENST00000411696.7	NP_001366588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF142	ENST00000411696.7	c.280+468G>A		intron_variant	Intron 4 of 10	5	NM_001379659.1	ENSP00000398798.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74486 AN: 151812 Hom.: 20493 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.490 AC: 74484 AN: 151930 Hom.: 20491 Cov.: 31 AF XY: 0.499 AC XY: 37023 AN XY: 74250

African (AFR) AF: 0.228 AC: 9435 AN: 41418

American (AMR) AF: 0.562 AC: 8592 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4233 AN: 5168

South Asian (SAS) AF: 0.675 AC: 3250 AN: 4816

European-Finnish (FIN) AF: 0.573 AC: 6039 AN: 10534

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38964 AN: 67926

Other (OTH) AF: 0.537 AC: 1134 AN: 2110

Alfa AF: 0.522 Hom.: 2726

Bravo AF: 0.476

Asia WGS AF: 0.705 AC: 2449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		0.16
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: rs3931102; hg19: chr2-219520405;