9-96818060-A-C

Position:

• chr9-96818060-A-C

Variant summary

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

The NM_001001662.3(ZNF782):​c.1963T>G​(p.Phe655Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF782 NM_001001662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF782	NM_001001662.3	c.1963T>G	p.Phe655Val	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.1963T>G	p.Phe655Val	missense_variant	6/6	1	NM_001001662.3	ENSP00000419397.1
ZNF782	ENST00000535338.5	c.1963T>G	p.Phe655Val	missense_variant	5/5	3		ENSP00000440624.2
ZNF782	ENST00000289032.12	n.1928T>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Nov 09, 2024

The c.1963T>G (p.F655V) alteration is located in exon 6 (coding exon 4) of the ZNF782 gene. This alteration results from a T to G substitution at nucleotide position 1963, causing the phenylalanine (F) at amino acid position 655 to be replaced by a valine (V). 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	0.98
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.4	M;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-6.5	D;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.50
MutPred		0.75		Gain of MoRF binding (P = 0.0752);Gain of MoRF binding (P = 0.0752);
MVP		0.78
MPC		0.59
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.81
gMVP		0.073

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: chr9-99580342;