14-102319770-C-G

Variant names:

• chr14-102319770-C-G
• NM_018335.6:c.5C>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.5C>G​(p.Ala2Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.218
• 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: 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=0.16805544).

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.5C>G	p.Ala2Gly	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.5C>G	p.Ala2Gly	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.5C>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Benign	0.97
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.22
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.23	B
Vest4		0.097
MutPred		0.25		Loss of stability (P = 0.0377)
MVP		0.13
MPC		0.085
ClinPred		0.85	D
GERP RS		2.2
PromoterAI		-0.80	Under-expression
gMVP		0.14
Mutation Taster		=95/5	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

hg19: chr14-102786107;