1-90982428-C-T

Position:

• chr1-90982428-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201269.3(ZNF644):​c.-17-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,160,318 control chromosomes in the GnomAD database, including 477,503 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 0.92 (64850 hom., cov: 31)
  • Exomes 𝑓: 0.90 (412653 hom.)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF644	NM_201269.3	c.-17-58G>A		intron_variant		ENST00000337393.10	NP_958357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10	c.-17-58G>A		intron_variant		1	NM_201269.3	ENSP00000337008	P1

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140045 AN: 151936 Hom.: 64794 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.929

GnomAD4 exome AF: 0.904 AC: 911296 AN: 1008264 Hom.: 412653 AF XY: 0.904 AC XY: 471979 AN XY: 522036

Gnomad4 AFR exome AF: 0.987

Gnomad4 AMR exome AF: 0.928

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.916

GnomAD4 genome AF: 0.922 AC: 140160 AN: 152054 Hom.: 64850 Cov.: 31 AF XY: 0.916 AC XY: 68093 AN XY: 74310

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.930

Alfa AF: 0.910 Hom.: 9217

Bravo AF: 0.937

Asia WGS AF: 0.967 AC: 3344 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs358691; hg19: chr1-91447985;