9-106924142-C-A

Position:

• chr9-106924142-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021224.6(ZNF462):​c.230C>A​(p.Ala77Glu) variant causes a missense change. 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: ZNF462 NM_021224.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

Genes affected

ZNF462 (HGNC:21684): (zinc finger protein 462) The protein encoded by this gene belongs to C2H2-type zinc finger family of proteins. It contains multiple C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20273131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF462	NM_021224.6	c.230C>A	p.Ala77Glu	missense_variant	3/13	ENST00000277225.10	NP_067047.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF462	ENST00000277225.10	c.230C>A	p.Ala77Glu	missense_variant	3/13	1	NM_021224.6	ENSP00000277225.5
ZNF462	ENST00000472574.1	c.230C>A	p.Ala77Glu	missense_variant	3/4	4		ENSP00000476222.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.230C>A (p.A77E) alteration is located in exon 3 (coding exon 2) of the ZNF462 gene. This alteration results from a C to A substitution at nucleotide position 230, causing the alanine (A) at amino acid position 77 to be replaced by a glutamic acid (E). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.21
Sift	Uncertain	0.0090	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.97	D;.
Vest4		0.52
MutPred		0.24		Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);
MVP		0.068
MPC		0.61
ClinPred		0.64	D
GERP RS		5.8
Varity_R		0.12
gMVP		0.59

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: chr9-109686423;