rs764501408

Variant names:

• chr14-102341817-A-G
• rs764501408
• NM_018335.6:c.2422A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018335.6(ZNF839):​c.2422A>G​(p.Ser808Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.17
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066177934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018335.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF839	NM_018335.6	MANE Select	c.2422A>G	p.Ser808Gly	missense	Exon 8 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.2272A>G	p.Ser758Gly	missense	Exon 7 of 7	NP_001371994.1
	ZNF839	NM_001267827.2		c.2074A>G	p.Ser692Gly	missense	Exon 8 of 8	NP_001254756.1	A8K0R7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.2422A>G	p.Ser808Gly	missense	Exon 8 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000557803.5	TSL:1	n.1669A>G		non_coding_transcript_exon	Exon 4 of 4
	ZNF839	ENST00000892181.1		c.2329A>G	p.Ser777Gly	missense	Exon 7 of 7	ENSP00000562240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.057
DANN	Benign	0.95
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.018
Sift	Benign	0.24	T
Sift4G	Uncertain	0.023	D
Polyphen		0.063	B
Vest4		0.13
MutPred		0.20		Gain of sheet (P = 0.0477)
MVP		0.11
MPC		0.089
ClinPred		0.17	T
GERP RS		-3.5
Varity_R		0.028
gMVP		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs764501408; hg19: chr14-102808154;