rs10922938

chr1-90938973-G-Achr1-90938973-G-C

Variant summary

Our verdict is Benign. Variant got -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. 12/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004531741).
• BS2: High AC in GnomAd at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.2381C>T	p.Ala794Val	missense_variant	3/6	ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.2381C>T	p.Ala794Val	missense_variant	3/6	1	NM_201269.3	P1

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

GnomAD3 exomes AF: 0.00102 AC: 256 AN: 250884 Hom.: 2 AF XY: 0.000671 AC XY: 91 AN XY: 135604

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.000693

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.000662

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

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000341 Hom.: 1

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 v4.3

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;T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0045	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.57	N;N;.
REVEL	Benign	0.053
Sift	Uncertain	0.014	D;D;.
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0020	B;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

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: rs10922938; hg19: chr1-91404530;