rs17131232

Variant names:

• chr1-90915548-T-A
• rs17131232
• NM_201269.3:c.*1250A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201269.3(ZNF644):​c.*1250A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 152,678 control chromosomes in the GnomAD database, including 315 homozygotes. 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: 𝑓 0.057 (314 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1 hom.)
• Consequence: ZNF644 NM_201269.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3	c.*1250A>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000337393.10	NP_958357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10	c.*1250A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_201269.3	ENSP00000337008.5
ZNF644	ENST00000347275.9	c.*1250A>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340828.5
ZNF644	ENST00000370440.5	c.*1250A>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000359469.1

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8719 AN: 152142 Hom.: 315 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0694 AC: 29 AN: 418 Hom.: 1 Cov.: 0 AF XY: 0.0630 AC XY: 16 AN XY: 254

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0704 AC: 29 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0572 AC: 8714 AN: 152260 Hom.: 314 Cov.: 32 AF XY: 0.0575 AC XY: 4280 AN XY: 74440

African (AFR) AF: 0.0201 AC: 837 AN: 41580

American (AMR) AF: 0.0712 AC: 1090 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3472

East Asian (EAS) AF: 0.0766 AC: 397 AN: 5184

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4828

European-Finnish (FIN) AF: 0.0553 AC: 587 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4976 AN: 67960

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0592 Hom.: 44

Bravo AF: 0.0577

Asia WGS AF: 0.0810 AC: 280 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.79
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs17131232; hg19: chr1-91381105;