9-96818410-T-G

Position:

• chr9-96818410-T-G

Variant summary

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

The NM_001001662.3(ZNF782):​c.1613A>C​(p.Gln538Pro) 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: 33)
• Consequence: ZNF782 NM_001001662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.361

Genes affected

ZNF782 (HGNC:33110): (zinc finger protein 782) Predicted to enable DNA-binding transcription activator 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2608484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF782	NM_001001662.3	c.1613A>C	p.Gln538Pro	missense_variant	6/6	ENST00000481138.6	NP_001001662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF782	ENST00000481138.6	c.1613A>C	p.Gln538Pro	missense_variant	6/6	1	NM_001001662.3	ENSP00000419397.1
ZNF782	ENST00000535338.5	c.1613A>C	p.Gln538Pro	missense_variant	5/5	3		ENSP00000440624.2
ZNF782	ENST00000289032.12	n.1578A>C		non_coding_transcript_exon_variant	3/3	2

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

Sep 09, 2024

The c.1613A>C (p.Q538P) alteration is located in exon 6 (coding exon 4) of the ZNF782 gene. This alteration results from a A to C substitution at nucleotide position 1613, causing the glutamine (Q) at amino acid position 538 to be replaced by a proline (P). 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	0.72
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.099
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.54		Gain of catalytic residue at Q538 (P = 0.0076);Gain of catalytic residue at Q538 (P = 0.0076);
MVP		0.44
MPC		0.52
ClinPred		0.92	D
GERP RS		2.3
Varity_R		0.55
gMVP		0.24

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: chr9-99580692;