Variant chr4-372924-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003441.4(ZNF141):c.487C>T(p.Arg163Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,613,932 control chromosomes in the GnomAD database, including 8 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

ZNF141
NM_003441.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.433

Variant links:

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 links:

ZNF141 (HGNC:):

ZNF141 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005369574).

BP6

Variant 4-372924-C-T is Benign according to our data. Variant chr4-372924-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 721178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-372924-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	4/4	ENST00000240499.8	NP_003432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF141	ENST00000240499.8 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	4/4	1	NM_003441.4	ENSP00000240499.7	Q15928
ZNF141	ENST00000512994.5 linkuse as main transcript	c.487C>T	p.Arg163Cys	missense_variant	4/5	1		ENSP00000425799.1	D6RIY0
ZNF141	ENST00000505939.5 linkuse as main transcript	c.227-10171C>T		intron_variant		5		ENSP00000424403.1	D6RB60
ZNF141	ENST00000366506.4 linkuse as main transcript	n.434C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

226

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00247

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00176

AC:

441

AN:

251056

Hom.:

AF XY:

0.00181

AC XY:

245

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00226

AC:

3296

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

1637

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00271

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.00148

AC:

226

AN:

152294

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00247

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00167

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00181

AC:

220

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 16, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.075

.;N

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.10

Sift

Benign

0.039

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.99

D;D

Vest4

0.14

MVP

0.25

MPC

0.23

ClinPred

0.036

GERP RS

1.2

Varity_R

0.086

gMVP

0.0070

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