9-96819401-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001662.3(ZNF782):c.622A>G(p.Ile208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF782 NM_001001662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0450

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06410211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF782	NM_001001662.3	c.622A>G	p.Ile208Val	missense_variant	6/6	ENST00000481138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF782	ENST00000481138.6	c.622A>G	p.Ile208Val	missense_variant	6/6	1	NM_001001662.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453680 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2 AN XY: 722844

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 18, 2023

The c.622A>G (p.I208V) alteration is located in exon 6 (coding exon 4) of the ZNF782 gene. This alteration results from a A to G substitution at nucleotide position 622, causing the isoleucine (I) at amino acid position 208 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	Benign	0.078
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.94
Dann	Benign	0.75
DEOGEN2	Benign	0.0029	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00017	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.38	N;.
REVEL	Benign	0.028
Sift	Benign	0.18	T;.
Sift4G	Benign	0.14	T;T
Polyphen		0.0010	B;B
Vest4		0.023
MutPred		0.37		Gain of disorder (P = 0.1648);Gain of disorder (P = 0.1648);
MVP		0.27
MPC		0.085
ClinPred		0.045	T
GERP RS		-3.1
Varity_R		0.036
gMVP		0.0065

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

LitVar

Other links and lift over

dbSNP: rs1850325513; hg19: chr9-99581683;