1-90917078-C-G

Position:

• chr1-90917078-C-G

Variant summary

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

The NM_201269.3(ZNF644):​c.3792-88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,357,176 control chromosomes in the GnomAD database, including 114 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 0.016 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (52 hom.)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

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=-0.82).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.3792-88G>C		intron_variant		ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.3792-88G>C		intron_variant		1	NM_201269.3	P1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2367 AN: 152122 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.00258 AC: 3107 AN: 1204936 Hom.: 52 AF XY: 0.00247 AC XY: 1499 AN XY: 605920

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.00390

Gnomad4 ASJ exome AF: 0.0205

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00129

Gnomad4 FIN exome AF: 0.0000395

Gnomad4 NFE exome AF: 0.000660

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.0156 AC: 2378 AN: 152240 Hom.: 62 Cov.: 32 AF XY: 0.0154 AC XY: 1148 AN XY: 74456

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00895 Hom.: 5

Bravo AF: 0.0174

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.78

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: rs17131234; hg19: chr1-91382635;