7-149210600-T-G

Position:

• chr7-149210600-T-G

Variant summary

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

The NM_003575.4(ZNF282):​c.848T>G​(p.Val283Gly) 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. 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)
• Consequence: ZNF282 NM_003575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.377

Genes affected

ZNF282 (HGNC:13076): (zinc finger protein 282) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located 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=0.06120515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF282	NM_003575.4	c.848T>G	p.Val283Gly	missense_variant	5/8	ENST00000610704.5
ZNF282	NM_001303481.3	c.848T>G	p.Val283Gly	missense_variant	5/9
ZNF282	XM_006716151.5	c.848T>G	p.Val283Gly	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF282	ENST00000610704.5	c.848T>G	p.Val283Gly	missense_variant	5/8	1	NM_003575.4	P1
ZNF282	ENST00000479907.1	c.848T>G	p.Val283Gly	missense_variant	5/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 01, 2023

The c.848T>G (p.V283G) alteration is located in exon 5 (coding exon 5) of the ZNF282 gene. This alteration results from a T to G substitution at nucleotide position 848, causing the valine (V) at amino acid position 283 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Uncertain	0.44	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.027
Sift	Uncertain	0.013	.;D
Sift4G	Uncertain	0.017	D;T
Polyphen		0.080	B;.
Vest4		0.13
MutPred		0.25		Loss of stability (P = 0.0141);Loss of stability (P = 0.0141);
MVP		0.11
ClinPred		0.11	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1796066811; hg19: chr7-148907692;