Variant 5-180849798-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001172638.2(ZFP62):c.1697G>T(p.Cys566Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000357 in 1,399,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000036 ( 0 hom. )

Consequence

ZFP62
NM_001172638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP62	NM_001172638.2 linkuse as main transcript	c.1697G>T	p.Cys566Phe	missense_variant	2/2	ENST00000502412.2	NP_001166109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP62	ENST00000502412.2 linkuse as main transcript	c.1697G>T	p.Cys566Phe	missense_variant	2/2	2	NM_001172638.2	ENSP00000423820	P3	Q8NB50-1
ZFP62	ENST00000506377.5 linkuse as main transcript	n.253+1583G>T		intron_variant, non_coding_transcript_variant		1
ZFP62	ENST00000512132.5 linkuse as main transcript	c.1598G>T	p.Cys533Phe	missense_variant	3/3	2		ENSP00000426193	A2	Q8NB50-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399610

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

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

Aug 28, 2023

The c.1697G>T (p.C566F) alteration is located in exon 2 (coding exon 2) of the ZFP62 gene. This alteration results from a G to T substitution at nucleotide position 1697, causing the cysteine (C) at amino acid position 566 to be replaced by a phenylalanine (F). 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

0.99

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.14

T;T

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

3.6

.;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-10

D;D

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0060

D;.

Polyphen

1.0

.;D

Vest4

0.63

MutPred

0.76

.;Loss of disorder (P = 0.0997);

MVP

0.99

ClinPred

1.0

GERP RS

4.3

Varity_R

0.91

gMVP

0.30

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