Variant 4-372807-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000240499.8(ZNF141):c.370A>G(p.Lys124Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,613,866 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.028 ( 202 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 211 hom. )

Consequence

ZNF141
ENST00000240499.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.548

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019043684).

BP6

Variant 4-372807-A-G is Benign according to our data. Variant chr4-372807-A-G is described in ClinVar as [Benign]. Clinvar id is 771138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.370A>G	p.Lys124Glu	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.370A>G	p.Lys124Glu	missense_variant	4/4	1	NM_003441.4	ENSP00000240499.7	Q15928
ZNF141	ENST00000512994.5 linkuse as main transcript	c.370A>G	p.Lys124Glu	missense_variant	4/5	1		ENSP00000425799.1	D6RIY0
ZNF141	ENST00000505939.5 linkuse as main transcript	c.227-10288A>G		intron_variant		5		ENSP00000424403.1	D6RB60
ZNF141	ENST00000366506.4 linkuse as main transcript	n.317A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4317

AN:

152200

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0985

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00763

AC:

1915

AN:

250924

Hom.:

AF XY:

0.00562

AC XY:

763

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00309

AC:

4517

AN:

1461548

Hom.:

211

Cov.:

AF XY:

0.00269

AC XY:

1955

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.000843

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000248

Gnomad4 OTH exome

AF:

0.00671

GnomAD4 genome

AF:

0.0284

AC:

4332

AN:

152318

Hom.:

202

Cov.:

AF XY:

0.0268

AC XY:

1996

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0986

Gnomad4 AMR

AF:

0.00921

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.0325

ESP6500AA

AF:

0.0985

AC:

434

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00964

AC:

1170

Asia WGS

AF:

0.00636

AC:

AN:

3476

EpiCase

AF:

0.000491

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

DANN

Benign

0.93

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.00044

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.037

Sift

Benign

0.12

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.88

P;B

Vest4

0.13

MVP

0.23

MPC

0.10

ClinPred

0.033

GERP RS

-2.4

Varity_R

0.11

gMVP

0.014

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