Genetic Variant ZNF737:p.Ala433Thr (chr19-20544906-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is . The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001159293.2(ZNF737):c.1297G>A(p.Ala433Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,609,268 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

ZNF737
NM_001159293.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.92

Publications

0 publications found

Variant links:

Genes affected

ZNF737 (HGNC:32468): (zinc finger protein 737) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF737 links:

ENSG00000269043 (HGNC:):

ENSG00000269043 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001159293.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.081).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159293.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF737	NM_001159293.2	MANE Select	c.1297G>A	p.Ala433Thr	missense	Exon 4 of 4	NP_001152765.1	O75373

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF737	ENST00000427401.9	TSL:2 MANE Select	c.1297G>A	p.Ala433Thr	missense	Exon 4 of 4	ENSP00000395733.3	O75373
ZNF737	ENST00000865229.1		c.1276G>A	p.Ala426Thr	missense	Exon 4 of 4	ENSP00000535288.1
ENSG00000269043	ENST00000653011.1		n.335-25033C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

148222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000554

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000169

AC:

AN:

248318

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000347

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000428

AC:

626

AN:

1461046

Hom.:

Cov.:

AF XY:

0.000405

AC XY:

294

AN XY:

726766

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.000126

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000520

AC:

578

AN:

1111576

Other (OTH)

AF:

0.000646

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000263

AC:

AN:

148222

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

AN XY:

72264

show subpopulations

African (AFR)

AF:

0.0000498

AC:

AN:

40170

American (AMR)

AF:

0.00

AC:

AN:

14802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

4972

South Asian (SAS)

AF:

0.00

AC:

AN:

4688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.000554

AC:

AN:

66772

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.000196

EpiCase

AF:

0.000491

EpiControl

AF:

0.000298

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.00011

LIST_S2

Benign

0.034

M_CAP

Benign

0.00070

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

-2.9

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.081

Sift

Benign

0.043

Sift4G

Benign

0.16

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.054

Mutation Taster

=94/6

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over