NM_201269.3:c.1212C>T

Variant names:

• chr1-90940142-G-A
• rs41286763
• NM_201269.3:c.1212C>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). Synonymous variant affecting the same amino acid position (i.e. T404T) has been classified as Uncertain significance.

• 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201269.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF644	NM_201269.3	MANE Select	c.1212C>T	p.Thr404Thr	synonymous	Exon 3 of 6	NP_958357.1	Q9H582-1
	ZNF644	NM_001437612.1		c.1212C>T	p.Thr404Thr	synonymous	Exon 5 of 9	NP_001424541.1
	ZNF644	NM_001437613.1		c.1212C>T	p.Thr404Thr	synonymous	Exon 3 of 7	NP_001424542.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF644	ENST00000337393.10	TSL:1 MANE Select	c.1212C>T	p.Thr404Thr	synonymous	Exon 3 of 6	ENSP00000337008.5	Q9H582-1
	ZNF644	ENST00000347275.9	TSL:1	c.23-21988C>T		intron	N/A	ENSP00000340828.5	Q9H582-3
	ZNF644	ENST00000370440.5	TSL:5	c.1212C>T	p.Thr404Thr	synonymous	Exon 3 of 6	ENSP00000359469.1	Q9H582-1

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZNF644-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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;