rs371235481

Variant names:

• chr14-102341607-T-C
• NM_018335.6:c.2212T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-102341607-T-C
• chr14-102341607-T-G

Variant summary

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

The NM_018335.6(ZNF839):​c.2212T>C​(p.Trp738Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W738G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=0.03278023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6	c.2212T>C	p.Trp738Arg	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.2212T>C	p.Trp738Arg	missense_variant	Exon 8 of 8	5	NM_018335.6	ENSP00000399863.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.86
DANN	Benign	0.46
DEOGEN2	Benign	0.0035	T;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.16	.;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.033	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.13	N;N;N;N
REVEL	Benign	0.027
Sift	Benign	0.37	T;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.013
MutPred		0.20		Gain of phosphorylation at S624 (P = 0.0835);Gain of phosphorylation at S624 (P = 0.0835);.;.;
MVP		0.081
MPC		0.15
ClinPred		0.13	T
GERP RS		-3.0
Varity_R		0.026
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-102807944;