rs367718180

Variant names:

• chr14-102341981-C-T
• rs367718180
• NM_018335.6:c.2586C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_018335.6(ZNF839):​c.2586C>T​(p.Ser862Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: ZNF839 NM_018335.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-102341981-C-T is Benign according to our data. Variant chr14-102341981-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.092 with no splicing effect.

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.2586C>T	p.Ser862Ser	synonymous	Exon 8 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.2436C>T	p.Ser812Ser	synonymous	Exon 7 of 7	NP_001371994.1
	ZNF839	NM_001267827.2		c.2238C>T	p.Ser746Ser	synonymous	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.2586C>T	p.Ser862Ser	synonymous	Exon 8 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000557803.5	TSL:1	n.1833C>T		non_coding_transcript_exon	Exon 4 of 4
	ZNF839	ENST00000892181.1		c.2493C>T	p.Ser831Ser	synonymous	Exon 7 of 7	ENSP00000562240.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000153 AC: 38 AN: 249106 AF XY: 0.000148

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000725 AC: 106 AN: 1461674 Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56 AN XY: 727124

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111852

Other (OTH) AF: 0.000133 AC: 8 AN: 60372

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

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

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000831

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.092

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: rs367718180; hg19: chr14-102808318;