chr7-149848227-C-A

Position:

• chr7-149848227-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099220.3(ZNF862):​c.734C>A​(p.Pro245Gln) 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: ZNF862 NM_001099220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13322371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF862	NM_001099220.3	c.734C>A	p.Pro245Gln	missense_variant	4/8	ENST00000223210.5	NP_001092690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF862	ENST00000223210.5	c.734C>A	p.Pro245Gln	missense_variant	4/8	5	NM_001099220.3	ENSP00000223210	P1
ZNF862	ENST00000488265.1	n.101C>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

Jun 01, 2023

The c.734C>A (p.P245Q) alteration is located in exon 4 (coding exon 4) of the ZNF862 gene. This alteration results from a C to A substitution at nucleotide position 734, causing the proline (P) at amino acid position 245 to be replaced by a glutamine (Q). 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	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.062
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.43	B
Vest4		0.28
MutPred		0.39		Loss of catalytic residue at P244 (P = 0.0117);
MVP		0.12
MPC		0.44
ClinPred		0.48	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.22

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: rs775923301; hg19: chr7-149545316;