rs41286763

chr1-90940142-G-Achr1-90940142-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_201269.3(ZNF644):c.1212C>T(p.Thr404=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.016 (235 hom.)
• Consequence: ZNF644 NM_201269.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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 GnomAd at 1702 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.1212C>T	p.Thr404=	synonymous_variant	3/6	ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.1212C>T	p.Thr404=	synonymous_variant	3/6	1	NM_201269.3	P1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1702 AN: 151908 Hom.: 14 Cov.: 32

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.: 37 AF XY: 0.0152 AC XY: 2059 AN XY: 135754

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.: 34 AF XY: 0.0160 AC XY: 11604 AN XY: 727186

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.: 14 Cov.: 32 AF XY: 0.0107 AC XY: 795 AN XY: 74326

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.: 14

Bravo AF: 0.0110

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.0193

EpiControl AF: 0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZNF644-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

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

Other links and lift over

dbSNP: rs41286763; hg19: chr1-91405699;