Variant 1-90938746-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_201269.3(ZNF644):c.2608A>G(p.Thr870Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,613,938 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 45 hom. )

Consequence

ZNF644
NM_201269.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004046917).

BP6

Variant 1-90938746-T-C is Benign according to our data. Variant chr1-90938746-T-C is described in ClinVar as [Benign]. Clinvar id is 780246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1924/152238) while in subpopulation AFR AF= 0.0438 (1819/41546). AF 95% confidence interval is 0.0421. There are 39 homozygotes in gnomad4. There are 917 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1924 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3 linkuse as main transcript	c.2608A>G	p.Thr870Ala	missense_variant	3/6	ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10 linkuse as main transcript	c.2608A>G	p.Thr870Ala	missense_variant	3/6	1	NM_201269.3	P1	Q9H582-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1917

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00336

AC:

842

AN:

250690

Hom.:

AF XY:

0.00242

AC XY:

328

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000972

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00132

AC:

1927

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

797

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0466

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000773

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.0126

AC:

1924

AN:

152238

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

917

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00996

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.0148

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0397

AC:

175

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00391

AC:

475

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.66

.;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.97

L;L;.

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.50

N;N;.

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;D;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.45

B;B;.

Vest4

0.13

MVP

0.30

MPC

0.38

ClinPred

0.048

GERP RS

3.1

Varity_R

0.050

gMVP

0.32

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