Genetic Variant NM_201269.3:c.3792-88G>A (chr1-90917078-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_201269.3(ZNF644):c.3792-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

ZNF644
NM_201269.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.943

Publications

0 publications found

Variant links:

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

ZNF644 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3 link	c.3792-88G>A		intron_variant	Intron 5 of 5	ENST00000337393.10	NP_958357.1	Q9H582-1A7E234

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF644	ENST00000337393.10 link	c.3792-88G>A		intron_variant	Intron 5 of 5	1	NM_201269.3	ENSP00000337008.5		Q9H582-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.30e-7

AC:

AN:

1204948

Hom.:

AF XY:

0.00000165

AC XY:

AN XY:

605928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27246

American (AMR)

AF:

0.00

AC:

AN:

36444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23586

East Asian (EAS)

AF:

0.00

AC:

AN:

36138

South Asian (SAS)

AF:

0.00

AC:

AN:

74348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4700

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

900222

Other (OTH)

AF:

0.00

AC:

AN:

51572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.0

(source)

DANN

Benign

0.61

PhyloP100

-0.94

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over