14-102341722-G-C

Variant names:

• chr14-102341722-G-C
• NM_018335.6:c.2327G>C

Variant summary

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

The NM_018335.6(ZNF839):​c.2327G>C​(p.Cys776Ser) 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: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.94

Genes affected

ZNF839 (HGNC:20345): (zinc finger protein 839) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CINP (HGNC:23789): (cyclin dependent kinase 2 interacting protein) The protein encoded by this gene is reported to be a component of the DNA replication complex as well as a genome-maintenance protein. It may interact with proteins important for replication initiation and has been shown to bind chromatin at the G1 phase of the cell cycle and dissociate from chromatin with replication initiation. It may also serve to regulate checkpoint signaling as part of the DNA damage response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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=0.067222476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6	c.2327G>C	p.Cys776Ser	missense_variant	Exon 8 of 8	ENST00000442396.7	NP_060805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF839	ENST00000442396.7	c.2327G>C	p.Cys776Ser	missense_variant	Exon 8 of 8	5	NM_018335.6	ENSP00000399863.2

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

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2327G>C (p.C776S) alteration is located in exon 8 (coding exon 8) of the ZNF839 gene. This alteration results from a G to C substitution at nucleotide position 2327, causing the cysteine (C) at amino acid position 776 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.016
DANN	Benign	0.49
DEOGEN2	Benign	0.0014	T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.26	.;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.013	B;B;B;.
Vest4		0.039
MutPred		0.35		Gain of glycosylation at C660 (P = 0.0292);Gain of glycosylation at C660 (P = 0.0292);.;.;
MVP		0.072
MPC		0.11
ClinPred		0.072	T
GERP RS		-4.3
Varity_R		0.031
gMVP		0.19

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: chr14-102808059;