Variant chr4-188003076-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000326866.5(ZFP42):c.269C>T(p.Ser90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,614,164 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

ZFP42
ENST00000326866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005326569).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP42	NM_174900.5 linkuse as main transcript	c.269C>T	p.Ser90Leu	missense_variant	4/4	ENST00000326866.5	NP_777560.2	Q96MM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP42	ENST00000326866.5 linkuse as main transcript	c.269C>T	p.Ser90Leu	missense_variant	4/4	1	NM_174900.5	ENSP00000317686.4	Q96MM3
ZFP42	ENST00000509524.5 linkuse as main transcript	c.269C>T	p.Ser90Leu	missense_variant	3/3	2		ENSP00000424662.1	Q96MM3
ZFP42	ENST00000618147.1 linkuse as main transcript	c.269C>T	p.Ser90Leu	missense_variant	1/1	6		ENSP00000483363.1	Q96MM3

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000656

AC:

165

AN:

251410

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000804

AC:

1175

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000774

AC XY:

563

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000966

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152286

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000627

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000684

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000771

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 24, 2021

The c.269C>T (p.S90L) alteration is located in exon 4 (coding exon 1) of the ZFP42 gene. This alteration results from a C to T substitution at nucleotide position 269, causing the serine (S) at amino acid position 90 to be replaced by a leucine (L). 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

0.43

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.5

DANN

Benign

0.64

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.48

.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.060

N;N;.

REVEL

Benign

0.063

Sift

Benign

0.67

T;T;.

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.034

MVP

0.014

MPC

0.093

ClinPred

0.0014

GERP RS

-1.7

Varity_R

0.024

gMVP

0.048

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