Genetic Variant NM_001159293.2:c.232T>G (chr19-20545971-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001159293.2(ZNF737):c.232T>G(p.Cys78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 1,540,878 control chromosomes in the GnomAD database, including 2,444 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 395 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2049 hom. )

Consequence

ZNF737
NM_001159293.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.892

Publications

12 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

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0028956234).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF737	NM_001159293.2 link	c.232T>G	p.Cys78Gly	missense_variant	Exon 4 of 4	ENST00000427401.9	NP_001152765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF737	ENST00000427401.9 link	c.232T>G	p.Cys78Gly	missense_variant	Exon 4 of 4	2	NM_001159293.2	ENSP00000395733.3

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9883

AN:

152154

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0758

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0525

Gnomad OTH

AF:

0.0583

GnomAD2 exomes

AF:

0.0498

AC:

9335

AN:

187382

AF XY:

0.0488

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0424

Gnomad EAS exome

AF:

0.000250

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0525

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0507

AC:

70421

AN:

1388608

Hom.:

2049

Cov.:

AF XY:

0.0500

AC XY:

34248

AN XY:

685118

show subpopulations

African (AFR)

AF:

0.114

AC:

3475

AN:

30580

American (AMR)

AF:

0.0247

AC:

746

AN:

30254

Ashkenazi Jewish (ASJ)

AF:

0.0376

AC:

790

AN:

21012

East Asian (EAS)

AF:

0.000127

AC:

AN:

39246

South Asian (SAS)

AF:

0.0375

AC:

2701

AN:

72022

European-Finnish (FIN)

AF:

0.0716

AC:

3619

AN:

50520

Middle Eastern (MID)

AF:

0.0380

AC:

206

AN:

5416

European-Non Finnish (NFE)

AF:

0.0518

AC:

56067

AN:

1082342

Other (OTH)

AF:

0.0491

AC:

2812

AN:

57216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3125

6251

9376

12502

15627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2130

4260

6390

8520

10650

<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:

0.0650

AC:

9897

AN:

152270

Hom.:

395

Cov.:

AF XY:

0.0651

AC XY:

4847

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.108

AC:

4478

AN:

41542

American (AMR)

AF:

0.0361

AC:

553

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0373

AC:

180

AN:

4828

European-Finnish (FIN)

AF:

0.0758

AC:

804

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0525

AC:

3574

AN:

68012

Other (OTH)

AF:

0.0577

AC:

122

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

478

956

1434

1912

2390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0518

Hom.:

925

Bravo

AF:

0.0637

TwinsUK

AF:

0.0445

AC:

165

ALSPAC

AF:

0.0550

AC:

212

ESP6500AA

AF:

0.104

AC:

144

ESP6500EA

AF:

0.0553

AC:

176

ExAC

AF:

0.0484

AC:

5847

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.51

T;D

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

M;.

PhyloP100

0.89

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-10

D;.

REVEL

Benign

0.028

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.036

D;.

Vest4

0.049

MPC

0.0040

ClinPred

0.079

GERP RS

-0.57

Varity_R

0.41

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