12-133105548-A-G

Position:

chr12-133105548-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003440.4(ZNF140):c.271A>G(p.Lys91Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,610,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

ZNF140
NM_003440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.115

Variant links:

Genes affected

ZNF140 (HGNC:12925): (zinc finger protein 140) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF140 links:

ZNF891 (HGNC:38709): (zinc finger protein 891) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF891 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037596494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF140	NM_003440.4 linkuse as main transcript	c.271A>G	p.Lys91Glu	missense_variant	5/5	ENST00000355557.7	NP_003431.2	P52738-1
ZNF891	NM_001277291.2 linkuse as main transcript	c.*14736T>C		3_prime_UTR_variant	2/2	ENST00000537226.3	NP_001264220.1	A8MT65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF140	ENST00000355557.7 linkuse as main transcript	c.271A>G	p.Lys91Glu	missense_variant	5/5	1	NM_003440.4	ENSP00000347755.2		P52738-1
ZNF891	ENST00000537226 linkuse as main transcript	c.*14736T>C		3_prime_UTR_variant	2/2	2	NM_001277291.2	ENSP00000437590.1		A8MT65

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000233

AC:

AN:

12890

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

7016

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.000359

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:

0.00

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

AF:

0.0000686

AC:

100

AN:

1458038

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

725182

show subpopulations

Gnomad4 AFR exome

AF:

0.00202

Gnomad4 AMR exome

AF:

0.000320

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000492

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000680

Hom.:

Bravo

AF:

0.000646

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 12, 2021

The c.271A>G (p.K91E) alteration is located in exon 5 (coding exon 4) of the ZNF140 gene. This alteration results from a A to G substitution at nucleotide position 271, causing the lysine (K) at amino acid position 91 to be replaced by a glutamic acid (E). 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

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.41

N;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;D;D;D

REVEL

Benign

0.036

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.075

MutPred

0.45

Loss of methylation at K91 (P = 0.0013);Loss of methylation at K91 (P = 0.0013);.;.;

MVP

0.22

MPC

0.60

ClinPred

0.0099

GERP RS

0.34

Varity_R

0.12

gMVP

0.053

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