Variant chr9-113042732-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003408.3(ZFP37):c.1886A>C(p.His629Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZFP37
NM_003408.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0220

Variant links:

Genes affected

ZFP37 (HGNC:12863): (ZFP37 zinc finger protein) This gene encodes a transcription factor that belongs to a large family of zinc finger proteins. A similar protein in mouse is thought to play a role in regulating the structures of the nucleolus and centromere in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ZFP37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11826682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFP37	NM_003408.3 linkuse as main transcript	c.1886A>C	p.His629Pro	missense_variant	4/4	ENST00000374227.8
ZFP37	NM_001282515.2 linkuse as main transcript	c.1931A>C	p.His644Pro	missense_variant	4/4
ZFP37	NM_001282518.2 linkuse as main transcript	c.1889A>C	p.His630Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP37	ENST00000374227.8 linkuse as main transcript	c.1886A>C	p.His629Pro	missense_variant	4/4	1	NM_003408.3		Q9Y6Q3-1
ZFP37	ENST00000555206.5 linkuse as main transcript	c.1889A>C	p.His630Pro	missense_variant	4/4	1			Q9Y6Q3-3
ZFP37	ENST00000553380.1 linkuse as main transcript	c.1931A>C	p.His644Pro	missense_variant	4/4	2		P1	Q9Y6Q3-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152056

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000241

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:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00177

AC:

2457

AN:

1386290

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1095

AN XY:

685332

show subpopulations

Gnomad4 AFR exome

AF:

0.00196

Gnomad4 AMR exome

AF:

0.000238

Gnomad4 ASJ exome

AF:

0.00101

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.000759

Gnomad4 FIN exome

AF:

0.000451

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Sep 29, 2022

The c.1886A>C (p.H629P) alteration is located in exon 4 (coding exon 4) of the ZFP37 gene. This alteration results from a A to C substitution at nucleotide position 1886, causing the histidine (H) at amino acid position 629 to be replaced by a proline (P). 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

Benign

0.081

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.5

DANN

Benign

0.81

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.13

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

3.0

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.076

Sift

Benign

0.23

T;T;T

Sift4G

Uncertain

0.049

D;D;T

Polyphen

0.0010

B;.;B

Vest4

0.24

MutPred

0.35

Gain of glycosylation at H629 (P = 0.0457);.;.;

MVP

0.12

MPC

0.13

ClinPred

0.14

GERP RS

1.9

Varity_R

0.22

gMVP

0.057

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