9-106924148-C-T

Position:

• chr9-106924148-C-T

Variant summary

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

The NM_021224.6(ZNF462):​c.236C>T​(p.Ser79Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF462 NM_021224.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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=0.09951916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF462	NM_021224.6	c.236C>T	p.Ser79Leu	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.236C>T	p.Ser79Leu	missense_variant	3/13	1	NM_021224.6	ENSP00000277225.5
ZNF462	ENST00000472574.1	c.236C>T	p.Ser79Leu	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

Nov 10, 2024

The c.236C>T (p.S79L) alteration is located in exon 3 (coding exon 2) of the ZNF462 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.85	N;.
REVEL	Benign	0.045
Sift	Benign	0.14	T;.
Sift4G	Uncertain	0.029	D;T
Polyphen		0.0	B;.
Vest4		0.083
MutPred		0.29		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.043
MPC		0.34
ClinPred		0.059	T
GERP RS		2.8
Varity_R		0.047
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr9-109686429;