14-102319860-G-A

Variant names:

• chr14-102319860-G-A
• rs908156355
• NM_018335.6:c.95G>A

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.95G>A​(p.Arg32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000977 in 1,125,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. R32L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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=0.09472838).

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.95G>A	p.Arg32His	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.95G>A	p.Arg32His	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.95G>A	p.Arg32His	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.95G>A	p.Arg32His	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.95G>A	p.Arg32His	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.95G>A	p.Arg32His	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000977 AC: 11 AN: 1125992 Hom.: 0 Cov.: 31 AF XY: 0.0000129 AC XY: 7 AN XY: 544280

African (AFR) AF: 0.0000433 AC: 1 AN: 23116

American (AMR) AF: 0.00 AC: 0 AN: 11734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16414

East Asian (EAS) AF: 0.0000382 AC: 1 AN: 26196

South Asian (SAS) AF: 0.0000309 AC: 1 AN: 32376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3074

European-Non Finnish (NFE) AF: 0.00000846 AC: 8 AN: 945302

Other (OTH) AF: 0.00 AC: 0 AN: 44758

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.11
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.038
Sift	Benign	0.075	T
Sift4G	Uncertain	0.037	D
Polyphen		0.79	P
Vest4		0.057
MutPred		0.46		Loss of methylation at R32 (P = 0.0416)
MVP		0.092
MPC		0.48
ClinPred		0.48	T
GERP RS		0.43
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.13
Mutation Taster		=97/3	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: rs908156355; hg19: chr14-102786197;