NM_201269.3:c.3792-88G>A

Variant names:

• chr1-90917078-C-T
• rs17131234
• NM_201269.3:c.3792-88G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201269.3(ZNF644):​c.3792-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.3792-88G>A		intron	N/A	NP_958357.1	Q9H582-1
	ZNF644	NM_001437612.1		c.3915-88G>A		intron	N/A	NP_001424541.1
	ZNF644	NM_001437613.1		c.3915-88G>A		intron	N/A	NP_001424542.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF644	ENST00000337393.10	TSL:1 MANE Select	c.3792-88G>A		intron	N/A	ENSP00000337008.5	Q9H582-1
	ZNF644	ENST00000347275.9	TSL:1	c.126-88G>A		intron	N/A	ENSP00000340828.5	Q9H582-3
	ZNF644	ENST00000370440.5	TSL:5	c.3792-88G>A		intron	N/A	ENSP00000359469.1	Q9H582-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1204948 Hom.: 0 AF XY: 0.00000165 AC XY: 1 AN XY: 605928

African (AFR) AF: 0.00 AC: 0 AN: 27246

American (AMR) AF: 0.00 AC: 0 AN: 36444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23586

East Asian (EAS) AF: 0.00 AC: 0 AN: 36138

South Asian (SAS) AF: 0.00 AC: 0 AN: 74348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4700

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 900222

Other (OTH) AF: 0.00 AC: 0 AN: 51572

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		-0.94

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: rs17131234; hg19: chr1-91382635;