rs1011423192

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-102319940-C-A
• chr14-102319940-C-G
• chr14-102319940-C-T

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.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. 14/20 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. P59A) has been classified as Uncertain significance.

• 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
• 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=0.18150708).

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.175C>A	p.Pro59Thr	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.175C>A	p.Pro59Thr	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.175C>A	p.Pro59Thr	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.175C>A	p.Pro59Thr	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.175C>A	p.Pro59Thr	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.175C>A	p.Pro59Thr	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18746 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

⚠️ 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: 20426

American (AMR) AF: 0.00 AC: 0 AN: 8904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12788

East Asian (EAS) AF: 0.00 AC: 0 AN: 18918

South Asian (SAS) AF: 0.0000341 AC: 1 AN: 29366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 898896

Other (OTH) AF: 0.00 AC: 0 AN: 39438

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
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
PhyloP100		1.2
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
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.11
Mutation Taster		=298/2	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: rs1011423192; hg19: chr14-102786277;