19-34943460-T-G

Position:

• chr19-34943460-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194325.3(ZNF30):​c.494T>G​(p.Ile165Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF30 NM_194325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.65

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]

ZNF30 (HGNC:):

ACMG classification

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=0.056183517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF30	NM_194325.3	c.494T>G	p.Ile165Arg	missense_variant	5/5	ENST00000601142.2	NP_919306.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF30	ENST00000601142.2	c.494T>G	p.Ile165Arg	missense_variant	5/5	2	NM_194325.3	ENSP00000469954.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248920 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135042

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.497T>G (p.I166R) alteration is located in exon 5 (coding exon 4) of the ZNF30 gene. This alteration results from a T to G substitution at nucleotide position 497, causing the isoleucine (I) at amino acid position 166 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.43
DANN	Benign	0.26
DEOGEN2	Benign	0.0086	.;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.22	.;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.48	.;.;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.91	.;N;.
REVEL	Benign	0.070
Sift	Benign	0.57	.;T;.
Sift4G	Benign	0.67	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.21
MutPred		0.34		.;.;Gain of disorder (P = 0.0107);
MVP		0.25
MPC		0.042
ClinPred		0.037	T
GERP RS		-4.3
Varity_R		0.037
gMVP		0.019

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

Other links and lift over

dbSNP: rs769841100; hg19: chr19-35434364;