Variant chr4-373410-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_003441.4(ZNF141):c.973A>T(p.Thr325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF141
NM_003441.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.191

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0031918883).

BP6

Variant 4-373410-A-T is Benign according to our data. Variant chr4-373410-A-T is described in ClinVar as [Benign]. Clinvar id is 403622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.973A>T	p.Thr325Ser	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.973A>T	p.Thr325Ser	missense_variant	4/4	1	NM_003441.4	ENSP00000240499	P1
ZNF141	ENST00000512994.5 linkuse as main transcript	c.570+403A>T		intron_variant		1		ENSP00000425799
ZNF141	ENST00000505939.5 linkuse as main transcript	c.227-9685A>T		intron_variant		5		ENSP00000424403

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000707

AC:

AN:

141426

Hom.:

AF XY:

0.0000780

AC XY:

AN XY:

76962

show subpopulations

Gnomad AFR exome

AF:

0.0000906

Gnomad AMR exome

AF:

0.0000444

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000572

Gnomad FIN exome

AF:

0.000321

Gnomad NFE exome

AF:

0.0000647

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727200

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000827

Hom.:

ExAC

AF:

0.0702

AC:

8524

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

DANN

Benign

0.94

DEOGEN2

Benign

0.048

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.048

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.085

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.018

Sift

Benign

0.46

Sift4G

Benign

0.95

Polyphen

0.034

Vest4

0.035

MutPred

0.24

Loss of glycosylation at T324 (P = 0.0868);

MPC

0.13

ClinPred

0.0056

GERP RS

-0.029

Varity_R

0.069

gMVP

0.010

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