rs354636

Variant names:

• chr1-91006936-A-G
• rs354636
• NM_201269.3:c.-18+15054T>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.-18+15054T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,146 control chromosomes in the GnomAD database, including 1,450 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 0.14 (1450 hom., cov: 31)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3	c.-18+15054T>C		intron_variant	Intron 1 of 5	ENST00000337393.10	NP_958357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10	c.-18+15054T>C		intron_variant	Intron 1 of 5	1	NM_201269.3	ENSP00000337008.5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20622 AN: 152028 Hom.: 1445 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20656 AN: 152146 Hom.: 1450 Cov.: 31 AF XY: 0.134 AC XY: 9993 AN XY: 74402

African (AFR) AF: 0.155 AC: 6444 AN: 41484

American (AMR) AF: 0.0860 AC: 1316 AN: 15294

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

East Asian (EAS) AF: 0.152 AC: 787 AN: 5174

South Asian (SAS) AF: 0.157 AC: 755 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1187 AN: 10590

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9048 AN: 68000

Other (OTH) AF: 0.132 AC: 278 AN: 2106

Alfa AF: 0.134 Hom.: 233

Bravo AF: 0.134

Asia WGS AF: 0.126 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
DANN	Benign	0.45
PhyloP100		-0.81
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: rs354636; hg19: chr1-91472493;