2-218650036-A-G

Variant names:

• chr2-218650036-A-G
• rs10187066
• NM_001379659.1:c.1048+323T>C

Variant summary

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

The NM_001379659.1(ZNF142):​c.1048+323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,144 control chromosomes in the GnomAD database, including 19,794 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 0.47 (19794 hom., cov: 32)
• Consequence: ZNF142 NM_001379659.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 28 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379659.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF142	NM_001379659.1	MANE Select	c.1048+323T>C		intron	N/A	NP_001366588.1	A0A7P0N7C4
	ZNF142	NM_001366290.3		c.1048+323T>C		intron	N/A	NP_001353219.1	A0A7P0N7C4
	ZNF142	NM_001379660.1		c.1048+323T>C		intron	N/A	NP_001366589.1	A0A7P0N7C4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF142	ENST00000411696.7	TSL:5 MANE Select	c.1048+323T>C		intron	N/A	ENSP00000398798.3	A0A7P0N7C4
	ZNF142	ENST00000449707.5	TSL:1	c.448+323T>C		intron	N/A	ENSP00000408643.1	P52746
	ZNF142	ENST00000450765.5	TSL:1	n.*273+323T>C		intron	N/A	ENSP00000397456.1	F2Z2H3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71034 AN: 152026 Hom.: 19795 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.467 AC: 71025 AN: 152144 Hom.: 19794 Cov.: 32 AF XY: 0.475 AC XY: 35318 AN XY: 74364

African (AFR) AF: 0.147 AC: 6115 AN: 41520

American (AMR) AF: 0.553 AC: 8457 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4241 AN: 5178

South Asian (SAS) AF: 0.674 AC: 3252 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 6046 AN: 10574

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38970 AN: 67974

Other (OTH) AF: 0.521 AC: 1101 AN: 2114

Alfa AF: 0.478 Hom.: 16489

Bravo AF: 0.449

Asia WGS AF: 0.699 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		0.15
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: rs10187066; hg19: chr2-219514759;