Variant 4-188003088-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174900.5(ZFP42):c.281C>A(p.Ser94Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ZFP42
NM_174900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.407

Variant links:

Genes affected

ZFP42 (HGNC:30949): (ZFP42 zinc finger protein) Enables sequence-specific double-stranded DNA binding activity. Involved in female gonad development and male gonad development. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZFP42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15963483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP42	NM_174900.5 linkuse as main transcript	c.281C>A	p.Ser94Tyr	missense_variant	4/4	ENST00000326866.5	NP_777560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZFP42	ENST00000326866.5 linkuse as main transcript	c.281C>A	p.Ser94Tyr	missense_variant	4/4	1	NM_174900.5	ENSP00000317686	P1
ZFP42	ENST00000509524.5 linkuse as main transcript	c.281C>A	p.Ser94Tyr	missense_variant	3/3	2		ENSP00000424662	P1
ZFP42	ENST00000618147.1 linkuse as main transcript	c.281C>A	p.Ser94Tyr	missense_variant	1/1			ENSP00000483363	P1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251388

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000468

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

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

Oct 29, 2021

The c.281C>A (p.S94Y) alteration is located in exon 4 (coding exon 1) of the ZFP42 gene. This alteration results from a C to A substitution at nucleotide position 281, causing the serine (S) at amino acid position 94 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Uncertain

0.50

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.37

.;.;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Benign

0.20

Sift

Benign

0.13

T;T;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.93

P;P;P

Vest4

0.091

MVP

0.19

MPC

0.55

ClinPred

0.68

GERP RS

3.6

Varity_R

0.15

gMVP

0.081

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