Variant 5-180849411-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001172638.2(ZFP62):c.2084A>C(p.His695Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,399,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

ZFP62
NM_001172638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

Genes affected

ZFP62 (HGNC:23241): (ZFP62 zinc finger protein) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP62 links:

ZFP62 (HGNC:):

ZFP62 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP62	NM_001172638.2 linkuse as main transcript	c.2084A>C	p.His695Pro	missense_variant	2/2	ENST00000502412.2	NP_001166109.1	Q8NB50-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP62	ENST00000502412.2 linkuse as main transcript	c.2084A>C	p.His695Pro	missense_variant	2/2	2	NM_001172638.2	ENSP00000423820.1	Q8NB50-1
ZFP62	ENST00000506377.5 linkuse as main transcript	n.254-1329A>C		intron_variant		1
ZFP62	ENST00000512132.5 linkuse as main transcript	c.1985A>C	p.His662Pro	missense_variant	3/3	2		ENSP00000426193.1	Q8NB50-3
ZFP62	ENST00000507843.1 linkuse as main transcript	n.106A>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

157838

Hom.:

AF XY:

0.0000360

AC XY:

AN XY:

83272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1399092

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

690016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

The c.2084A>C (p.H695P) alteration is located in exon 2 (coding exon 2) of the ZFP62 gene. This alteration results from a A to C substitution at nucleotide position 2084, causing the histidine (H) at amino acid position 695 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.062

.;T

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.10

T;T

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Pathogenic

3.7

.;H

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;.

Polyphen

1.0

.;D

Vest4

0.55

MutPred

0.75

.;Gain of glycosylation at H695 (P = 0.0418);

MVP

0.90

ClinPred

0.90

GERP RS

4.6

Varity_R

0.75

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over