NM_018335.6:c.212A>G

Variant names:

• chr14-102319977-A-G
• rs2073033399
• NM_018335.6:c.212A>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.212A>G​(p.Asp71Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,017,130 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.726
• 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=0.22048983).

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.212A>G	p.Asp71Gly	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.212A>G	p.Asp71Gly	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.212A>G	p.Asp71Gly	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.212A>G	p.Asp71Gly	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.212A>G	p.Asp71Gly	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.212A>G	p.Asp71Gly	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000197 AC: 2 AN: 1017130 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 484896

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20232

American (AMR) AF: 0.000166 AC: 1 AN: 6014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10756

East Asian (EAS) AF: 0.00 AC: 0 AN: 19456

South Asian (SAS) AF: 0.00 AC: 0 AN: 19380

European-Finnish (FIN) AF: 0.0000619 AC: 1 AN: 16148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 884256

Other (OTH) AF: 0.00 AC: 0 AN: 38350

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Benign	0.97
Eigen	Benign	0.12
Eigen_PC	Benign	0.051
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.73
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.073
Sift	Benign	0.051	T
Sift4G	Benign	0.068	T
Polyphen		0.96	D
Vest4		0.24
MutPred		0.26		Gain of methylation at R70 (P = 0.0338)
MVP		0.51
MPC		0.40
ClinPred		0.58	D
GERP RS		2.7
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.10
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

dbSNP: rs2073033399; hg19: chr14-102786314;