1-90940142-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_201269.3(ZNF644):​c.1212C>A​(p.Thr404Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. T404T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF644 NM_201269.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.

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>A	p.Thr404Thr	synonymous	Exon 3 of 6	NP_958357.1	Q9H582-1
	ZNF644	NM_001437612.1		c.1212C>A	p.Thr404Thr	synonymous	Exon 5 of 9	NP_001424541.1
	ZNF644	NM_001437613.1		c.1212C>A	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>A	p.Thr404Thr	synonymous	Exon 3 of 6	ENSP00000337008.5	Q9H582-1
	ZNF644	ENST00000347275.9	TSL:1	c.23-21988C>A		intron	N/A	ENSP00000340828.5	Q9H582-3
	ZNF644	ENST00000370440.5	TSL:5	c.1212C>A	p.Thr404Thr	synonymous	Exon 3 of 6	ENSP00000359469.1	Q9H582-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.11
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;