Variant 19-20624438-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001076675.3(ZNF626):c.1439C>A(p.Pro480His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P480S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 8)

Exomes 𝑓: 0.000043 ( 9 hom. )

Failed GnomAD Quality Control

Consequence

ZNF626
NM_001076675.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF626 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30635965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3 linkuse as main transcript	c.1439C>A	p.Pro480His	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6 linkuse as main transcript	c.1439C>A	p.Pro480His	missense_variant	4/4	4	NM_001076675.3	P1	Q68DY1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

152206

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000489

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000923

Gnomad NFE exome

AF:

0.0000298

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000426

AC:

AN:

634056

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

325568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000809

Gnomad4 ASJ exome

AF:

0.000135

Gnomad4 EAS exome

AF:

0.000183

Gnomad4 SAS exome

AF:

0.0000568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000283

Gnomad4 OTH exome

AF:

0.0000996

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.1439C>A (p.P480H) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a C to A substitution at nucleotide position 1439, causing the proline (P) at amino acid position 480 to be replaced by a histidine (H). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.10

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.021

M_CAP

Benign

0.0020

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.99

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.32

MutPred

0.40

Loss of catalytic residue at P480 (P = 0.0898);

MVP

0.48

MPC

0.21

ClinPred

0.36

GERP RS

-1.7

Varity_R

0.16

gMVP

0.028

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