Variant 19-20544933-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001159293.2(ZNF737):c.1270C>T(p.Pro424Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,613,014 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 3 hom. )

Consequence

ZNF737
NM_001159293.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045717567).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF737	NM_001159293.2 linkuse as main transcript	c.1270C>T	p.Pro424Ser	missense_variant	4/4	ENST00000427401.9
LOC105372316	XR_936408.3 linkuse as main transcript	n.279-25006G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF737	ENST00000427401.9 linkuse as main transcript	c.1270C>T	p.Pro424Ser	missense_variant	4/4	2	NM_001159293.2	P1
	ENST00000653011.1 linkuse as main transcript	n.335-25006G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000540

AC:

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000536

AC:

133

AN:

248184

Hom.:

AF XY:

0.000571

AC XY:

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000800

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000882

Gnomad OTH exome

AF:

0.000998

GnomAD4 exome

AF:

0.000718

AC:

1049

AN:

1461006

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

556

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000822

Gnomad4 OTH exome

AF:

0.000928

GnomAD4 genome

AF:

0.000539

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000894

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000627

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2021

The c.1270C>T (p.P424S) alteration is located in exon 4 (coding exon 4) of the ZNF737 gene. This alteration results from a C to T substitution at nucleotide position 1270, causing the proline (P) at amino acid position 424 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.84

M_CAP

Benign

0.0018

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.66

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.098

Sift

Uncertain

0.010

Sift4G

Uncertain

0.036

Vest4

0.14

MVP

0.11

MPC

0.0054

ClinPred

0.052

GERP RS

0.80

Varity_R

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over