rs2073027016

Variant names:

• chr14-102319901-G-A
• NM_018335.6:c.136G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-102319901-G-A
• chr14-102319901-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018335.6(ZNF839):​c.136G>A​(p.Glu46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,121,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10508838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6	c.136G>A	p.Glu46Lys	missense_variant	Exon 1 of 8	ENST00000442396.7	NP_060805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF839	ENST00000442396.7	c.136G>A	p.Glu46Lys	missense_variant	Exon 1 of 8	5	NM_018335.6	ENSP00000399863.2
ZNF839	ENST00000558850.5	c.-61+2235G>A		intron_variant	Intron 1 of 7	2		ENSP00000453363.1
ZNF839	ENST00000559185.5	c.-61+383G>A		intron_variant	Intron 1 of 7	2		ENSP00000453109.1
ZNF839	ENST00000559098.5	n.-57G>A		upstream_gene_variant		2		ENSP00000453515.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1121360 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 546068

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: 0.00000214

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
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.041
Sift	Benign	0.15	T
Sift4G	Uncertain	0.020	D
Polyphen		0.70	P
Vest4		0.092
MutPred		0.29		Gain of MoRF binding (P = 0.0029);
MVP		0.20
MPC		0.14
ClinPred		0.72	D
GERP RS		0.69
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr14-102786238;