Variant 9-113043195-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003408.3(ZFP37):c.1423C>T(p.His475Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZFP37
NM_003408.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046467304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFP37	NM_003408.3 linkuse as main transcript	c.1423C>T	p.His475Tyr	missense_variant	4/4	ENST00000374227.8
ZFP37	NM_001282515.2 linkuse as main transcript	c.1468C>T	p.His490Tyr	missense_variant	4/4
ZFP37	NM_001282518.2 linkuse as main transcript	c.1426C>T	p.His476Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP37	ENST00000374227.8 linkuse as main transcript	c.1423C>T	p.His475Tyr	missense_variant	4/4	1	NM_003408.3		Q9Y6Q3-1
ZFP37	ENST00000555206.5 linkuse as main transcript	c.1426C>T	p.His476Tyr	missense_variant	4/4	1			Q9Y6Q3-3
ZFP37	ENST00000553380.1 linkuse as main transcript	c.1468C>T	p.His490Tyr	missense_variant	4/4	2		P1	Q9Y6Q3-2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250642

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461528

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000145

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Nov 17, 2023

The c.1423C>T (p.H475Y) alteration is located in exon 4 (coding exon 4) of the ZFP37 gene. This alteration results from a C to T substitution at nucleotide position 1423, causing the histidine (H) at amino acid position 475 to be replaced by a tyrosine (Y). 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

0.45

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.098

T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.00024

LIST_S2

Benign

0.052

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

N;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.087

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.072

B;.;B

Vest4

0.20

MVP

0.23

MPC

0.47

ClinPred

0.18

GERP RS

3.4

Varity_R

0.29

gMVP

0.12

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