dbSNP rs1188952: ZNF644:c.*676C>T (chr1-90916122-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_201269.3(ZNF644):c.*676C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.121 in 152,508 control chromosomes in the GnomAD database, including 1,167 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 0.12 ( 1164 hom., cov: 32)

Exomes 𝑓: 0.088 ( 3 hom. )

Consequence

ZNF644
NM_201269.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88

Publications

11 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF644	NM_201269.3 link	c.*676C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000337393.10	NP_958357.1	Q9H582-1A7E234

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF644	ENST00000337393.10 link	c.*676C>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_201269.3	ENSP00000337008.5	Q9H582-1
ZNF644	ENST00000347275.9 link	c.*676C>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000340828.5	Q9H582-3
ZNF644	ENST00000370440.5 link	c.*676C>T	3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000359469.1	Q9H582-1
ZNF644	ENST00000361321.5 link	c.*676C>T	downstream_gene_variant		2		ENSP00000354659.5	Q9H582-3

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18446

AN:

151946

Hom.:

1167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.0878

AC:

AN:

444

Hom.:

Cov.:

AF XY:

0.0821

AC XY:

AN XY:

268

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0892

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.121

AC:

18447

AN:

152064

Hom.:

1164

Cov.:

AF XY:

0.120

AC XY:

8900

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.106

AC:

4387

AN:

41510

American (AMR)

AF:

0.0801

AC:

1224

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3466

East Asian (EAS)

AF:

0.152

AC:

785

AN:

5180

South Asian (SAS)

AF:

0.156

AC:

753

AN:

4816

European-Finnish (FIN)

AF:

0.113

AC:

1193

AN:

10566

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9012

AN:

67916

Other (OTH)

AF:

0.122

AC:

257

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

815

1630

2446

3261

4076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.125

Hom.:

747

Bravo

AF:

0.117

Asia WGS

AF:

0.116

AC:

400

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over