19-34944075-A-C

Position:

• chr19-34944075-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194325.3(ZNF30):​c.1109A>C​(p.Lys370Thr) 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. 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: 0.140

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36381996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF30	NM_194325.3	c.1109A>C	p.Lys370Thr	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.1109A>C	p.Lys370Thr	missense_variant	5/5	2	NM_194325.3	ENSP00000469954	P1
ZNF30	ENST00000303586.11	c.1112A>C	p.Lys371Thr	missense_variant	5/5	1		ENSP00000303889
ZNF30	ENST00000439785.5	c.1112A>C	p.Lys371Thr	missense_variant	5/5	5		ENSP00000403441
ZNF30	ENST00000601957.5	c.*928A>C		3_prime_UTR_variant	6/6	2		ENSP00000470094

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

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

Mar 31, 2023

The c.1112A>C (p.K371T) alteration is located in exon 5 (coding exon 4) of the ZNF30 gene. This alteration results from a A to C substitution at nucleotide position 1112, causing the lysine (K) at amino acid position 371 to be replaced by a threonine (T). 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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.55	.;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;.;M
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.6	.;D;.
REVEL	Benign	0.037
Sift	Uncertain	0.0010	.;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.22
MutPred		0.57		.;.;Loss of methylation at K370 (P = 0.0054);
MVP		0.66
MPC		0.23
ClinPred		0.97	D
GERP RS		2.1
Varity_R		0.35
gMVP		0.018

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35434979;