rs41286763

Variant names:

• chr1-90940142-G-A
• rs41286763
• NM_201269.3:c.1212C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-90940142-G-A
• chr1-90940142-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.46
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1699 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3	c.1212C>T	p.Thr404Thr	synonymous_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	c.1212C>T	p.Thr404Thr	synonymous_variant	Exon 3 of 6	1	NM_201269.3	ENSP00000337008.5

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

GnomAD2 exomes AF: 0.0142 AC: 3574 AN: 251192 AF XY: 0.0152

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 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

African (AFR) AF: 0.00242 AC: 81 AN: 33478

American (AMR) AF: 0.00897 AC: 401 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 413 AN: 26134

East Asian (EAS) AF: 0.0106 AC: 422 AN: 39696

South Asian (SAS) AF: 0.0240 AC: 2073 AN: 86252

European-Finnish (FIN) AF: 0.00410 AC: 219 AN: 53396

Middle Eastern (MID) AF: 0.0368 AC: 212 AN: 5768

European-Non Finnish (NFE) AF: 0.0161 AC: 17900 AN: 1111944

Other (OTH) AF: 0.0158 AC: 957 AN: 60390

GnomAD4 genome AF: 0.0112 AC: 1699 AN: 152026 Hom.: 14 Cov.: 32 AF XY: 0.0107 AC XY: 795 AN XY: 74326

African (AFR) AF: 0.00301 AC: 125 AN: 41488

American (AMR) AF: 0.00787 AC: 120 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5178

South Asian (SAS) AF: 0.0208 AC: 100 AN: 4802

European-Finnish (FIN) AF: 0.00284 AC: 30 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 67946

Other (OTH) AF: 0.0138 AC: 29 AN: 2106

Alfa AF: 0.0154 Hom.: 48

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: no assertion criteria provided

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
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs41286763; hg19: chr1-91405699;