9-96818705-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001001662.3(ZNF782):c.1318C>T(p.His440Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 8.75

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF782	NM_001001662.3	c.1318C>T	p.His440Tyr	missense_variant	6/6	ENST00000481138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF782	ENST00000481138.6	c.1318C>T	p.His440Tyr	missense_variant	6/6	1	NM_001001662.3	P1
ZNF782	ENST00000535338.5	c.1318C>T	p.His440Tyr	missense_variant	5/5	3		P1
ZNF782	ENST00000289032.12	n.1283C>T		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

Jan 02, 2024

The c.1318C>T (p.H440Y) alteration is located in exon 6 (coding exon 4) of the ZNF782 gene. This alteration results from a C to T substitution at nucleotide position 1318, causing the histidine (H) at amino acid position 440 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.6	H;H
MutationTaster	Benign	0.53	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.53
MutPred		0.79		Loss of disorder (P = 0.0366);Loss of disorder (P = 0.0366);
MVP		0.94
MPC		0.55
ClinPred		1.0	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		0.27

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: chr9-99580987;