Genetic Variant ZFP62:p.Asp648Asn (chr5-180849553-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172638.2(ZFP62):c.1942G>A(p.Asp648Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ZFP62
NM_001172638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05801046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP62	NM_001172638.2 link	c.1942G>A	p.Asp648Asn	missense_variant	Exon 2 of 2	ENST00000502412.2	NP_001166109.1	Q8NB50-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP62	ENST00000502412.2 link	c.1942G>A	p.Asp648Asn	missense_variant	Exon 2 of 2	2	NM_001172638.2	ENSP00000423820.1	Q8NB50-1
ZFP62	ENST00000506377.5 link	n.254-1471G>A		intron_variant	Intron 3 of 3	1
ZFP62	ENST00000512132.5 link	c.1843G>A	p.Asp615Asn	missense_variant	Exon 3 of 3	2		ENSP00000426193.1	Q8NB50-3
ZFP62	ENST00000507843.1 link	n.-37G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1399974

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690454

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1942G>A (p.D648N) alteration is located in exon 2 (coding exon 2) of the ZFP62 gene. This alteration results from a G to A substitution at nucleotide position 1942, causing the aspartic acid (D) at amino acid position 648 to be replaced by an asparagine (N). 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

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0016

.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.44

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.090

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.065

.;B

Vest4

0.19

MutPred

0.22

.;Loss of ubiquitination at K652 (P = 0.0331);

MVP

0.27

ClinPred

0.36

GERP RS

4.6

Varity_R

0.045

gMVP

0.061

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over