19-34933719-C-G

Variant names:

• chr19-34933719-C-G
• NM_194325.3:c.252C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194325.3(ZNF30):​c.252C>G​(p.Cys84Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF30 NM_194325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.181
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08700329).

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.252C>G	p.Cys84Trp	missense	Exon 4 of 5	NP_919306.2	P17039-1
	ZNF30	NM_001099437.2		c.255C>G	p.Cys85Trp	missense	Exon 4 of 5	NP_001092907.1	P17039-2
	ZNF30	NM_001099438.2		c.255C>G	p.Cys85Trp	missense	Exon 4 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.252C>G	p.Cys84Trp	missense	Exon 4 of 5	ENSP00000469954.1	P17039-1
	ZNF30	ENST00000303586.11	TSL:1	c.255C>G	p.Cys85Trp	missense	Exon 4 of 5	ENSP00000303889.7	P17039-2
	ZNF30	ENST00000439785.5	TSL:5	c.255C>G	p.Cys85Trp	missense	Exon 4 of 5	ENSP00000403441.1	P17039-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.1
DANN	Benign	0.34
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.093	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.18
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.036
Sift	Benign	0.16	T
Sift4G	Benign	0.089	T
Polyphen		0.032	B
Vest4		0.31
MutPred		0.35		Gain of MoRF binding (P = 0.0148)
MVP		0.23
MPC		0.036
ClinPred		0.035	T
GERP RS		-2.8
Varity_R		0.057
gMVP		0.039
Mutation Taster		=97/3	polymorphism

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

hg19: chr19-35424623;