19-21057539-A-T

Position:

• chr19-21057539-A-T

Variant summary

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

The NM_025189.4(ZNF430):​c.1231A>T​(p.Asn411Tyr) 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. 14/21 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: ZNF430 NM_025189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.110

Genes affected

ZNF430 (HGNC:20808): (zinc finger protein 430) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in substantia nigra development. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06456205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF430	NM_025189.4	c.1231A>T	p.Asn411Tyr	missense_variant	5/5	ENST00000261560.10	NP_079465.3
ZNF430	NM_001172671.2	c.1228A>T	p.Asn410Tyr	missense_variant	5/5		NP_001166142.1
ZNF430	XM_047439464.1	c.1138A>T	p.Asn380Tyr	missense_variant	4/4		XP_047295420.1
ZNF430	XM_047439465.1	c.1135A>T	p.Asn379Tyr	missense_variant	4/4		XP_047295421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF430	ENST00000261560.10	c.1231A>T	p.Asn411Tyr	missense_variant	5/5	1	NM_025189.4	ENSP00000261560	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jan 23, 2023

The c.1231A>T (p.N411Y) alteration is located in exon 5 (coding exon 5) of the ZNF430 gene. This alteration results from a A to T substitution at nucleotide position 1231, causing the asparagine (N) at amino acid position 411 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.3
DANN	Benign	0.92
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.045	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.79	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.012
Sift	Benign	0.050	D
Sift4G	Benign	0.11	T
Polyphen		0.020	B
Vest4		0.13
MutPred		0.27		Loss of disorder (P = 0.0562);
MVP		0.048
MPC		0.19
ClinPred		0.062	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.026

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: chr19-21240345;