Variant chr1-90938699-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_201269.3(ZNF644):c.2655G>T(p.Glu885Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,613,136 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 43 hom., cov: 32)

Exomes 𝑓: 0.030 ( 861 hom. )

Consequence

ZNF644
NM_201269.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.539

Variant links:

Genes affected

ZNF644 (HGNC:29222): (zinc finger protein 644) The protein encoded by this gene is a zinc finger transcription factor that may play a role in eye development. Defects in this gene have been associated with high myopia. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ZNF644 links:

ZNF644 (HGNC:):

ZNF644 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019966662).

BP6

Variant 1-90938699-C-A is Benign according to our data. Variant chr1-90938699-C-A is described in ClinVar as [Benign]. Clinvar id is 3038400.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3359/152204) while in subpopulation NFE AF= 0.033 (2241/67970). AF 95% confidence interval is 0.0318. There are 43 homozygotes in gnomad4. There are 1604 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF644	NM_201269.3 linkuse as main transcript	c.2655G>T	p.Glu885Asp	missense_variant	3/6	ENST00000337393.10	NP_958357.1	Q9H582-1A7E234

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10 linkuse as main transcript	c.2655G>T	p.Glu885Asp	missense_variant	3/6	1	NM_201269.3	ENSP00000337008.5		Q9H582-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3361

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00594

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0524

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.0222

AC:

5544

AN:

250098

Hom.:

112

AF XY:

0.0219

AC XY:

2966

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.00463

Gnomad AMR exome

AF:

0.00692

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.0490

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0304

AC:

44342

AN:

1460932

Hom.:

861

Cov.:

AF XY:

0.0294

AC XY:

21350

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00416

Gnomad4 AMR exome

AF:

0.00816

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00315

Gnomad4 FIN exome

AF:

0.0479

Gnomad4 NFE exome

AF:

0.0351

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0221

AC:

3359

AN:

152204

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1604

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0524

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0280

Hom.:

124

Bravo

AF:

0.0191

TwinsUK

AF:

0.0351

AC:

130

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.0311

AC:

267

ExAC

AF:

0.0221

AC:

2687

EpiCase

AF:

0.0264

EpiControl

AF:

0.0278

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF644-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.4

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.79

.;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.63

N;N;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.41

N;N;.

REVEL

Benign

0.17

Sift

Benign

0.12

T;T;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.043

MutPred

0.28

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;

MPC

0.22

ClinPred

0.012

GERP RS

0.47

Varity_R

0.035

gMVP

0.25

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