rs41286761

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

myopia 21, autosomal dominant
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ZNF644 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3359 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3 link	c.2655G>T	p.Glu885Asp	missense_variant	Exon 3 of 6	ENST00000337393.10	NP_958357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10 link	c.2655G>T	p.Glu885Asp	missense_variant	Exon 3 of 6	1	NM_201269.3	ENSP00000337008.5

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

GnomAD2 exomes

AF:

0.0222

AC:

5544

AN:

250098

AF XY:

0.0219

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 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

African (AFR)

AF:

0.00416

AC:

139

AN:

33408

American (AMR)

AF:

0.00816

AC:

364

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

467

AN:

26100

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.00315

AC:

270

AN:

85842

European-Finnish (FIN)

AF:

0.0479

AC:

2555

AN:

53392

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0351

AC:

39076

AN:

1111786

Other (OTH)

AF:

0.0240

AC:

1450

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2447

4893

7340

9786

12233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1446

2892

4338

5784

7230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0221

AC:

3359

AN:

152204

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1604

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00592

AC:

246

AN:

41546

American (AMR)

AF:

0.0120

AC:

183

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00269

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0524

AC:

556

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0330

AC:

2241

AN:

67970

Other (OTH)

AF:

0.0147

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0284

Hom.:

255

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

Dec 20, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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;.

PhyloP100

-0.54

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over