1-90918032-T-G

Variant names:

• chr1-90918032-T-G
• rs2448020
• NM_201269.3:c.3791+20A>C

Variant summary

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

The NM_201269.3(ZNF644):​c.3791+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,587,532 control chromosomes in the GnomAD database, including 13,560 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 0.11 (1055 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12505 hom.)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

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.3791+20A>C		intron	N/A	NP_958357.1	Q9H582-1
	ZNF644	NM_001437612.1		c.3914+20A>C		intron	N/A	NP_001424541.1
	ZNF644	NM_001437613.1		c.3914+20A>C		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.3791+20A>C		intron	N/A	ENSP00000337008.5	Q9H582-1
	ZNF644	ENST00000347275.9	TSL:1	c.125+20A>C		intron	N/A	ENSP00000340828.5	Q9H582-3
	ZNF644	ENST00000370440.5	TSL:5	c.3791+20A>C		intron	N/A	ENSP00000359469.1	Q9H582-1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17382 AN: 152110 Hom.: 1058 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.121 AC: 30327 AN: 251074 AF XY: 0.124

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.0533

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.129 AC: 185096 AN: 1435306 Hom.: 12505 Cov.: 25 AF XY: 0.130 AC XY: 93043 AN XY: 715742

African (AFR) AF: 0.0758 AC: 2495 AN: 32914

American (AMR) AF: 0.0572 AC: 2558 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5077 AN: 25968

East Asian (EAS) AF: 0.116 AC: 4607 AN: 39556

South Asian (SAS) AF: 0.154 AC: 13192 AN: 85762

European-Finnish (FIN) AF: 0.112 AC: 5973 AN: 53400

Middle Eastern (MID) AF: 0.161 AC: 919 AN: 5720

European-Non Finnish (NFE) AF: 0.131 AC: 142196 AN: 1087798

Other (OTH) AF: 0.136 AC: 8079 AN: 59504

GnomAD4 genome AF: 0.114 AC: 17384 AN: 152226 Hom.: 1055 Cov.: 32 AF XY: 0.113 AC XY: 8430 AN XY: 74434

African (AFR) AF: 0.0813 AC: 3380 AN: 41552

American (AMR) AF: 0.0773 AC: 1181 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 741 AN: 3472

East Asian (EAS) AF: 0.151 AC: 781 AN: 5178

South Asian (SAS) AF: 0.156 AC: 752 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1190 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9018 AN: 68000

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.124 Hom.: 1505

Bravo AF: 0.109

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.44
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2448020; hg19: chr1-91383589; COSMIC: COSV61346547;