dbSNP rs41286763: ZNF644:p.Thr404Thr (chr1-90940142-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_201269.3(ZNF644):c.1212C>T(p.Thr404Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,806 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 32)

Exomes 𝑓: 0.016 ( 235 hom. )

Consequence

ZNF644
NM_201269.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.46

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-90940142-G-A is Benign according to our data. Variant chr1-90940142-G-A is described in ClinVar as [Benign]. Clinvar id is 3057105.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0112 (1699/152026) while in subpopulation SAS AF= 0.0208 (100/4802). AF 95% confidence interval is 0.0175. There are 14 homozygotes in gnomad4. There are 795 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1699 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3 link	c.1212C>T	p.Thr404Thr	synonymous_variant	Exon 3 of 6	ENST00000337393.10	NP_958357.1	Q9H582-1A7E234

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10 link	c.1212C>T	p.Thr404Thr	synonymous_variant	Exon 3 of 6	1	NM_201269.3	ENSP00000337008.5		Q9H582-1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1702

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00788

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0208

Gnomad FIN

AF:

0.00284

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0142

AC:

3574

AN:

251192

Hom.:

AF XY:

0.0152

AC XY:

2059

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.00865

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0151

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0155

AC:

22678

AN:

1461780

Hom.:

235

Cov.:

AF XY:

0.0160

AC XY:

11604

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00897

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.0240

Gnomad4 FIN exome

AF:

0.00410

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0112

AC:

1699

AN:

152026

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

795

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00787

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.0208

Gnomad4 FIN

AF:

0.00284

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0193

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF644-related disorder

Benign:1

Mar 20, 2019

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

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.67

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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