1-90938973-G-A

Variant names:

• chr1-90938973-G-A
• rs10922938
• NM_201269.3:c.2381C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_201269.3(ZNF644):​c.2381C>T​(p.Ala794Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,613,902 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A794T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0036 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: ZNF644 NM_201269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004531741).
• BS2: High AC in GnomAd4 at 554 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF644	NM_201269.3	MANE Select	c.2381C>T	p.Ala794Val	missense	Exon 3 of 6	NP_958357.1
	ZNF644	NM_001437612.1		c.2381C>T	p.Ala794Val	missense	Exon 5 of 9	NP_001424541.1
	ZNF644	NM_001437613.1		c.2381C>T	p.Ala794Val	missense	Exon 3 of 7	NP_001424542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF644	ENST00000337393.10	TSL:1 MANE Select	c.2381C>T	p.Ala794Val	missense	Exon 3 of 6	ENSP00000337008.5
	ZNF644	ENST00000347275.9	TSL:1	c.23-20819C>T		intron	N/A	ENSP00000340828.5
	ZNF644	ENST00000370440.5	TSL:5	c.2381C>T	p.Ala794Val	missense	Exon 3 of 6	ENSP00000359469.1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152082 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00102 AC: 256 AN: 250884 AF XY: 0.000671

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000391 AC: 572 AN: 1461702 Hom.: 2 Cov.: 33 AF XY: 0.000337 AC XY: 245 AN XY: 727150

African (AFR) AF: 0.0138 AC: 463 AN: 33472

American (AMR) AF: 0.000693 AC: 31 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53352

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111934

Other (OTH) AF: 0.000662 AC: 40 AN: 60388

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152200 Hom.: 6 Cov.: 32 AF XY: 0.00349 AC XY: 260 AN XY: 74422

African (AFR) AF: 0.0127 AC: 529 AN: 41528

American (AMR) AF: 0.00118 AC: 18 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67980

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00127 Hom.: 2

Bravo AF: 0.00418

ESP6500AA AF: 0.0134 AC: 59

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00125 AC: 152

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.053
Sift	Uncertain	0.014	D
Sift4G	Benign	0.16	T
Polyphen		0.0020	B
Vest4		0.091
MVP		0.34
MPC		0.24
ClinPred		0.0043	T
GERP RS		3.9
Varity_R		0.049
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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: rs10922938; hg19: chr1-91404530;