7-149848299-G-A

Variant summary

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

The NM_001099220.3(ZNF862):c.806G>A(p.Gly269Glu) 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. 15/21 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: ZNF862 NM_001099220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.335

Genes affected

ZNF862 (HGNC:34519): (zinc finger protein 862) Predicted to enable metal ion binding activity and protein dimerization activity. Predicted to be involved in regulation of transcription, DNA-templated. 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=0.05418089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF862	NM_001099220.3	c.806G>A	p.Gly269Glu	missense_variant	4/8	ENST00000223210.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF862	ENST00000223210.5	c.806G>A	p.Gly269Glu	missense_variant	4/8	5	NM_001099220.3	P1
ZNF862	ENST00000488265.1	n.173G>A		non_coding_transcript_exon_variant	1/2	3

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

Apr 22, 2022

The c.806G>A (p.G269E) alteration is located in exon 4 (coding exon 4) of the ZNF862 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the glycine (G) at amino acid position 269 to be replaced by a glutamic acid (E). 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	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	10
Dann	Benign	0.94
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.045
Sift	Benign	0.27	T
Sift4G	Uncertain	0.024	D
Polyphen		0.18	B
Vest4		0.099
MutPred		0.34		Loss of loop (P = 0.0603);
MVP		0.12
MPC		0.21
ClinPred		0.22	T
GERP RS		3.0
Varity_R		0.047
gMVP		0.33

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: chr7-149545388;