chr19-34931867-G-T

Variant names:

• chr19-34931867-G-T
• rs202087912
• NM_194325.3:c.34G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194325.3(ZNF30):​c.34G>T​(p.Gly12*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF30 NM_194325.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 4 publications found

Genes affected

ZNF30 (HGNC:13090): (zinc finger protein 30) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194325.3. 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
	ZNF30	NM_194325.3	MANE Select	c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	NP_919306.2	P17039-1
	ZNF30	NM_001099437.2		c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	NP_001092907.1	P17039-2
	ZNF30	NM_001099438.2		c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	NP_001092908.1	P17039-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF30	ENST00000601142.2	TSL:2 MANE Select	c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	ENSP00000469954.1	P17039-1
	ZNF30	ENST00000303586.11	TSL:1	c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	ENSP00000303889.7	P17039-2
	ZNF30	ENST00000439785.5	TSL:5	c.34G>T	p.Gly12*	stop_gained	Exon 3 of 5	ENSP00000403441.1	P17039-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459638 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726082

⚠️ 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: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 85730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111294

Other (OTH) AF: 0.00 AC: 0 AN: 60312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.52
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.51	D
PhyloP100		2.3
Vest4		0.079
GERP RS		1.6
Mutation Taster		=130/70	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs202087912; hg19: chr19-35422771;