chr14-102319940-C-A

Variant names:

• chr14-102319940-C-A
• rs1011423192
• NM_018335.6:c.175C>A

Variant summary

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

The NM_018335.6(ZNF839):​c.175C>A​(p.Pro59Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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: 9.5e-7 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=0.18150708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6	c.175C>A	p.Pro59Thr	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.175C>A	p.Pro59Thr	missense_variant	Exon 1 of 8	5	NM_018335.6	ENSP00000399863.2
ZNF839	ENST00000558850.5	c.-61+2274C>A		intron_variant	Intron 1 of 7	2		ENSP00000453363.1
ZNF839	ENST00000559185.5	c.-61+422C>A		intron_variant	Intron 1 of 7	2		ENSP00000453109.1
ZNF839	ENST00000559098.5	n.-18C>A		upstream_gene_variant		2		ENSP00000453515.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049184 Hom.: 0 Cov.: 30 AF XY: 0.00000197 AC XY: 1 AN XY: 506640

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: 0.0000341

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.80
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.067
Sift	Benign	0.43	T
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.28		Gain of catalytic residue at P54 (P = 0.0038);
MVP		0.28
MPC		0.39
ClinPred		0.58	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs1011423192; hg19: chr14-102786277;