chr14-102341551-A-G

Variant names:

• chr14-102341551-A-G
• rs1245098874
• NM_018335.6:c.2156A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018335.6(ZNF839):​c.2156A>G​(p.Gln719Arg) 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. 15/22 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0760
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09075037).

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.2156A>G	p.Gln719Arg	missense	Exon 8 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.2006A>G	p.Gln669Arg	missense	Exon 7 of 7	NP_001371994.1
	ZNF839	NM_001267827.2		c.1808A>G	p.Gln603Arg	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.2156A>G	p.Gln719Arg	missense	Exon 8 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000557803.5	TSL:1	n.1403A>G		non_coding_transcript_exon	Exon 4 of 4
	ZNF839	ENST00000892181.1		c.2063A>G	p.Gln688Arg	missense	Exon 7 of 7	ENSP00000562240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726240

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111068

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		-0.076
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.010
Sift	Benign	0.27	T
Sift4G	Benign	0.20	T
Polyphen		0.089	B
Vest4		0.13
MutPred		0.33		Gain of helix (P = 0.132)
MVP		0.072
MPC		0.12
ClinPred		0.29	T
GERP RS		-4.3
Varity_R		0.038
gMVP		0.18
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1245098874; hg19: chr14-102807888;