7-149223884-A-C

Position:

• chr7-149223884-A-C

Variant summary

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

The NM_003575.4(ZNF282):​c.1253A>C​(p.Gln418Pro) 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: -4.35

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=0.06334248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF282	NM_003575.4	c.1253A>C	p.Gln418Pro	missense_variant	8/8	ENST00000610704.5
ZNF282	NM_001303481.3	c.1253A>C	p.Gln418Pro	missense_variant	8/9
ZNF282	XM_006716151.5	c.1256A>C	p.Gln419Pro	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF282	ENST00000610704.5	c.1253A>C	p.Gln418Pro	missense_variant	8/8	1	NM_003575.4	P1
ZNF282	ENST00000479907.1	c.1253A>C	p.Gln418Pro	missense_variant	8/9	2
ZNF282	ENST00000470381.1	n.351A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 21, 2023

The c.1253A>C (p.Q418P) alteration is located in exon 8 (coding exon 8) of the ZNF282 gene. This alteration results from a A to C substitution at nucleotide position 1253, causing the glutamine (Q) at amino acid position 418 to be replaced by a proline (P). 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	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.83
DANN	Benign	0.13
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.63	T
Sift4G	Benign	0.27	T;T
Polyphen		0.034	B;.
Vest4		0.14
MutPred		0.35		Gain of glycosylation at Q418 (P = 5e-04);Gain of glycosylation at Q418 (P = 5e-04);
MVP		0.092
ClinPred		0.12	T
GERP RS		-0.47
Varity_R		0.099
gMVP		0.14

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: chr7-148920976;