9-96818155-C-A

Position:

• chr9-96818155-C-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.1868G>T​(p.Cys623Phe) variant causes a missense change. 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: 6.93

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, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF782	NM_001001662.3	c.1868G>T	p.Cys623Phe	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.1868G>T	p.Cys623Phe	missense_variant	6/6	1	NM_001001662.3	ENSP00000419397.1
ZNF782	ENST00000535338.5	c.1868G>T	p.Cys623Phe	missense_variant	5/5	3		ENSP00000440624.2
ZNF782	ENST00000289032.12	n.1833G>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

Mar 19, 2024

The c.1868G>T (p.C623F) alteration is located in exon 6 (coding exon 4) of the ZNF782 gene. This alteration results from a G to T substitution at nucleotide position 1868, causing the cysteine (C) at amino acid position 623 to be replaced by a phenylalanine (F). 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	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	4.1	H;H
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-11	D;.
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.70		Gain of MoRF binding (P = 0.1034);Gain of MoRF binding (P = 0.1034);
MVP		0.93
MPC		0.64
ClinPred		1.0	D
GERP RS		3.1
Varity_R		0.93
gMVP		0.12

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: chr9-99580437;