chr5-180849553-C-T

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

19

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]

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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
ZFP62NM_001172638.2 linkc.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 Appris UniProt
ZFP62ENST00000502412.2 linkc.1942G>A p.Asp648Asn missense_variant Exon 2 of 2 2 NM_001172638.2 ENSP00000423820.1 Q8NB50-1
ZFP62ENST00000506377.5 linkn.254-1471G>A intron_variant Intron 3 of 3 1
ZFP62ENST00000512132.5 linkc.1843G>A p.Asp615Asn missense_variant Exon 3 of 3 2 ENSP00000426193.1 Q8NB50-3
ZFP62ENST00000507843.1 linkn.-37G>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1399974
Hom.:
0
Cov.:
78
AF XY:
0.00000145
AC XY:
1
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.:
33

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
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.0016
.;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
.;L
PrimateAI
Benign
0.44
T
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
T
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.

Other links and lift over

hg19: chr5-180276553; API