Variant rs587776959 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_003441.4(ZNF141):c.1421C>T(p.Thr474Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF141
NM_003441.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 0.155

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-373858-C-T is Pathogenic according to our data. Variant chr4-373858-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 50294.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.1421C>T	p.Thr474Ile	missense_variant	4/4	ENST00000240499.8	NP_003432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF141	ENST00000240499.8 linkuse as main transcript	c.1421C>T	p.Thr474Ile	missense_variant	4/4	1	NM_003441.4	ENSP00000240499	P1
ZNF141	ENST00000512994.5 linkuse as main transcript	c.570+851C>T		intron_variant		1		ENSP00000425799
ZNF141	ENST00000505939.5 linkuse as main transcript	c.227-9237C>T		intron_variant		5		ENSP00000424403

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239408

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130374

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:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445834

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718690

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Polydactyly, postaxial, type A6

Pathogenic:2

Likely pathogenic, no assertion criteria provided	literature only	ClinVar Staff, National Center for Biotechnology Information (NCBI)	Jun 27, 2013	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.0066

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.082

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MutPred

0.48

Gain of stability (P = 0.0106);

MVP

0.25

MPC

0.39

ClinPred

0.96

GERP RS

-0.24

Varity_R

0.24

gMVP

0.023

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