Genetic Variant NM_201269.3:c.-17-58G>A (chr1-90982428-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_201269.3(ZNF644):c.-17-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,160,318 control chromosomes in the GnomAD database, including 477,503 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 0.92 ( 64850 hom., cov: 31)

Exomes 𝑓: 0.90 ( 412653 hom. )

Consequence

ZNF644
NM_201269.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.379

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3 link	c.-17-58G>A		intron_variant	Intron 1 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.-17-58G>A		intron_variant	Intron 1 of 5	1	NM_201269.3	ENSP00000337008.5		Q9H582-1

Frequencies

GnomAD3 genomes

AF:

0.922

AC:

140045

AN:

151936

Hom.:

64794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.921

Gnomad AMR

AF:

0.941

Gnomad ASJ

AF:

0.945

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.924

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.929

GnomAD4 exome

AF:

0.904

AC:

911296

AN:

1008264

Hom.:

412653

AF XY:

0.904

AC XY:

471979

AN XY:

522036

show subpopulations

African (AFR)

AF:

0.987

AC:

24509

AN:

24844

American (AMR)

AF:

0.928

AC:

40683

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

21946

AN:

23288

East Asian (EAS)

AF:

1.00

AC:

37354

AN:

37366

South Asian (SAS)

AF:

0.916

AC:

70300

AN:

76730

European-Finnish (FIN)

AF:

0.767

AC:

35224

AN:

45922

Middle Eastern (MID)

AF:

0.952

AC:

4666

AN:

4902

European-Non Finnish (NFE)

AF:

0.900

AC:

634965

AN:

705882

Other (OTH)

AF:

0.916

AC:

41649

AN:

45478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4330

8659

12989

17318

21648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10812

21624

32436

43248

54060

<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

AF:

0.922

AC:

140160

AN:

152054

Hom.:

64850

Cov.:

AF XY:

0.916

AC XY:

68093

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.984

AC:

40871

AN:

41548

American (AMR)

AF:

0.941

AC:

14384

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.945

AC:

3278

AN:

3468

East Asian (EAS)

AF:

0.999

AC:

5178

AN:

5182

South Asian (SAS)

AF:

0.923

AC:

4449

AN:

4822

European-Finnish (FIN)

AF:

0.756

AC:

7961

AN:

10530

Middle Eastern (MID)

AF:

0.969

AC:

285

AN:

294

European-Non Finnish (NFE)

AF:

0.898

AC:

60954

AN:

67908

Other (OTH)

AF:

0.930

AC:

1960

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

536

1073

1609

2146

2682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.910

Hom.:

9217

Bravo

AF:

0.937

Asia WGS

AF:

0.967

AC:

3344

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

(source)

DANN

Benign

0.39

PhyloP100

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over