12-133084132-A-T

Variant names:

• chr12-133084132-A-T
• rs632610
• NM_003440.4:c.232+571A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 6 publications found

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]

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003440.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF140	NM_003440.4	MANE Select	c.232+571A>T		intron	N/A	NP_003431.2
	ZNF140	NM_001300776.2		c.-78+571A>T		intron	N/A	NP_001287705.1	P52738-2
	ZNF140	NM_001300778.2		c.-145+571A>T		intron	N/A	NP_001287707.1	P52738-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF140	ENST00000355557.7	TSL:1 MANE Select	c.232+571A>T		intron	N/A	ENSP00000347755.2	P52738-1
	ZNF140	ENST00000536790.5	TSL:1	n.232+571A>T		intron	N/A	ENSP00000441170.1	F5GX08
	ZNF140	ENST00000880216.1		c.232+571A>T		intron	N/A	ENSP00000550275.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000739 AC: 2 AN: 270674 Hom.: 0 Cov.: 0 AF XY: 0.0000128 AC XY: 2 AN XY: 155990

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

African (AFR) AF: 0.00 AC: 0 AN: 6184

American (AMR) AF: 0.0000557 AC: 1 AN: 17962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9450

East Asian (EAS) AF: 0.00 AC: 0 AN: 8310

South Asian (SAS) AF: 0.00 AC: 0 AN: 52086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2616

European-Non Finnish (NFE) AF: 0.00000669 AC: 1 AN: 149386

Other (OTH) AF: 0.00 AC: 0 AN: 12748

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
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

Other links and lift over

dbSNP: rs632610; hg19: chr12-133660718;