Variant chr1-90937874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_201269.3(ZNF644):c.3299G>A(p.Arg1100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,878 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 8 hom. )

Consequence

ZNF644
NM_201269.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009139836).

BP6

Variant 1-90937874-C-T is Benign according to our data. Variant chr1-90937874-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 715422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-90937874-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF644	NM_201269.3 linkuse as main transcript	c.3299G>A	p.Arg1100His	missense_variant	4/6	ENST00000337393.10	NP_958357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10 linkuse as main transcript	c.3299G>A	p.Arg1100His	missense_variant	4/6	1	NM_201269.3	ENSP00000337008	P1	Q9H582-1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00275

AC:

689

AN:

250794

Hom.:

AF XY:

0.00286

AC XY:

387

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00495

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00411

AC:

6009

AN:

1461602

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

2882

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.00255

Gnomad4 NFE exome

AF:

0.00490

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152276

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.00309

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00299

AC:

363

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00498

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ZNF644: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.039

T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.70

MVP

0.29

MPC

0.97

ClinPred

0.015

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.43

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