10-43644586-C-T

Variant names:

• chr10-43644586-C-T
• NM_006973.3:c.286G>A

Variant summary

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

The NM_006973.3(ZNF32):​c.286G>A​(p.Glu96Lys) 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. 12/21 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: ZNF32 NM_006973.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0590

Genes affected

ZNF32 (HGNC:13095): (zinc finger protein 32) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF32-AS3 (HGNC:):

ZNF32-AS1 (HGNC:23577): (ZNF32 antisense RNA 1)

ZNF32-AS3 (HGNC:23583): (ZNF32 antisense RNA 3)

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=0.25429916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF32	NM_006973.3	c.286G>A	p.Glu96Lys	missense_variant	Exon 3 of 3	ENST00000374433.7	NP_008904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF32	ENST00000374433.7	c.286G>A	p.Glu96Lys	missense_variant	Exon 3 of 3	1	NM_006973.3	ENSP00000363556.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286G>A (p.E96K) alteration is located in exon 3 (coding exon 2) of the ZNF32 gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glutamic acid (E) at amino acid position 96 to be replaced by a lysine (K). 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	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	0.089
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.070	N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.89	P;P
Vest4		0.15
MutPred		0.44		Gain of methylation at E96 (P = 0.0053);Gain of methylation at E96 (P = 0.0053);
MVP		0.14
MPC		0.70
ClinPred		0.73	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.26

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: chr10-44140034;