rs528027695

Variant names:

• chr14-102341403-A-G
• rs528027695
• NM_018335.6:c.2008A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018335.6(ZNF839):​c.2008A>G​(p.Ser670Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,574,852 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0440
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024269015).

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.2008A>G	p.Ser670Gly	missense	Exon 8 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.1858A>G	p.Ser620Gly	missense	Exon 7 of 7	NP_001371994.1
	ZNF839	NM_001267827.2		c.1660A>G	p.Ser554Gly	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.2008A>G	p.Ser670Gly	missense	Exon 8 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000557803.5	TSL:1	n.1255A>G		non_coding_transcript_exon	Exon 4 of 4
	ZNF839	ENST00000892181.1		c.1915A>G	p.Ser639Gly	missense	Exon 7 of 7	ENSP00000562240.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000774 AC: 17 AN: 219504 AF XY: 0.0000841

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000355

Gnomad ASJ exome AF: 0.000140

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000520 AC: 74 AN: 1422674 Hom.: 0 Cov.: 30 AF XY: 0.0000738 AC XY: 52 AN XY: 704464

African (AFR) AF: 0.00 AC: 0 AN: 32070

American (AMR) AF: 0.0000265 AC: 1 AN: 37678

Ashkenazi Jewish (ASJ) AF: 0.0000428 AC: 1 AN: 23372

East Asian (EAS) AF: 0.00 AC: 0 AN: 39278

South Asian (SAS) AF: 0.000836 AC: 68 AN: 81330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092722

Other (OTH) AF: 0.0000683 AC: 4 AN: 58546

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000662 AC: 8

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	0.071
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.96
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.044
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.026
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.0050	B
Vest4		0.045
MutPred		0.12		Loss of glycosylation at S554 (P = 0.044)
MVP		0.14
MPC		0.11
ClinPred		0.023	T
GERP RS		-1.6
Varity_R		0.070
gMVP		0.18
Mutation Taster		=98/2	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: rs528027695; hg19: chr14-102807740;