Genetic Variant ZNF140:c.232+571A>T (chr12-133084132-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003440.4(ZNF140):c.232+571A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000739 in 270,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

ZNF140
NM_003440.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

6 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF140	NM_003440.4 link	c.232+571A>T		intron_variant	Intron 4 of 4	ENST00000355557.7	NP_003431.2	P52738-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF140	ENST00000355557.7 link	c.232+571A>T		intron_variant	Intron 4 of 4	1	NM_003440.4	ENSP00000347755.2		P52738-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000739

AC:

AN:

270674

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

155990

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6184

American (AMR)

AF:

0.0000557

AC:

AN:

17962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9450

East Asian (EAS)

AF:

0.00

AC:

AN:

8310

South Asian (SAS)

AF:

0.00

AC:

AN:

52086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2616

European-Non Finnish (NFE)

AF:

0.00000669

AC:

AN:

149386

Other (OTH)

AF:

0.00

AC:

AN:

12748

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.88

(source)

DANN

Benign

0.56

PhyloP100

0.086

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over