chr14-102319827-C-G

Variant names:

• chr14-102319827-C-G
• rs2139438074
• NM_018335.6:c.62C>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.62C>G​(p.Pro21Arg) 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. 14/20 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)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.175
• 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]

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=0.05294183).

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.62C>G	p.Pro21Arg	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.62C>G	p.Pro21Arg	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.62C>G	p.Pro21Arg	missense	Exon 1 of 8	NP_001372001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.62C>G	p.Pro21Arg	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.62C>G	p.Pro21Arg	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.62C>G	p.Pro21Arg	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.6
DANN	Benign	0.86
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.17
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.51	N
REVEL	Benign	0.027
Sift	Benign	0.066	T
Sift4G	Uncertain	0.017	D
Polyphen		0.0020	B
Vest4		0.087
MutPred		0.25		Gain of catalytic residue at G17 (P = 0.0016)
MVP		0.17
MPC		0.090
ClinPred		0.13	T
GERP RS		0.43
PromoterAI		-0.00070	Neutral
gMVP		0.21
Mutation Taster		=93/7	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: rs2139438074; hg19: chr14-102786164;