Variant rs7254995 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C78S) has been classified as Likely benign.

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

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZNF737	NM_001159293.2 linkuse as main transcript	c.232T>G	p.Cys78Gly	missense_variant	4/4	ENST00000427401.9
LOC105372316	XR_936408.3 linkuse as main transcript	n.279-23968A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF737	ENST00000427401.9 linkuse as main transcript	c.232T>G	p.Cys78Gly	missense_variant	4/4	2	NM_001159293.2	P1
	ENST00000653011.1 linkuse as main transcript	n.335-23968A>C		intron_variant, non_coding_transcript_variant
ZNF737	ENST00000594419.1 linkuse as main transcript	c.40T>G	p.Cys14Gly	missense_variant	3/3	3
ZNF737	ENST00000597940.1 linkuse as main transcript	c.*198T>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	5

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

GnomAD3 exomes

AF:

0.0498

AC:

9335

AN:

187382

Hom.:

294

AF XY:

0.0488

AC XY:

4891

AN XY:

100126

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 SAS exome

AF:

0.0420

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

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0247

Gnomad4 ASJ exome

AF:

0.0376

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0375

Gnomad4 FIN exome

AF:

0.0716

Gnomad4 NFE exome

AF:

0.0518

Gnomad4 OTH exome

AF:

0.0491

GnomAD4 genome

AF:

0.0650

AC:

9897

AN:

152270

Hom.:

395

Cov.:

AF XY:

0.0651

AC XY:

4847

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0373

Gnomad4 FIN

AF:

0.0758

Gnomad4 NFE

AF:

0.0525

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0506

Hom.:

433

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

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;.

MutationTaster

Benign

1.0

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over