chr7-149844724-G-C

Position:

• chr7-149844724-G-C

Variant summary

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

The NM_001099220.3(ZNF862):​c.124G>C​(p.Val42Leu) 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: 33)
• Consequence: ZNF862 NM_001099220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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=0.07552004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF862	NM_001099220.3	c.124G>C	p.Val42Leu	missense_variant	2/8	ENST00000223210.5	NP_001092690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF862	ENST00000223210.5	c.124G>C	p.Val42Leu	missense_variant	2/8	5	NM_001099220.3	ENSP00000223210	P1
ZNF862	ENST00000460379.1	c.-129G>C		5_prime_UTR_variant	2/4	4		ENSP00000417450
ZNF862	ENST00000489820.5	n.187G>C		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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 07, 2022

The c.124G>C (p.V42L) alteration is located in exon 2 (coding exon 2) of the ZNF862 gene. This alteration results from a G to C substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.23	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.075
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0010	B
Vest4		0.073
MutPred		0.51		Loss of helix (P = 0.0626);
MVP		0.030
MPC		0.17
ClinPred		0.26	T
GERP RS		3.0
Varity_R		0.084
gMVP		0.12

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: chr7-149541813;