14-102319937-C-T

Variant names:

• chr14-102319937-C-T
• rs1251720215
• NM_018335.6:c.172C>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.172C>T​(p.Pro58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,058,236 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• 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=0.09925106).

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.172C>T	p.Pro58Ser	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.172C>T	p.Pro58Ser	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.172C>T	p.Pro58Ser	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.172C>T	p.Pro58Ser	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.172C>T	p.Pro58Ser	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.172C>T	p.Pro58Ser	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000382 AC: 1 AN: 26182 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: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1058236 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 512182

⚠️ 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: 20704

American (AMR) AF: 0.00 AC: 0 AN: 11144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13408

East Asian (EAS) AF: 0.00 AC: 0 AN: 18748

South Asian (SAS) AF: 0.00 AC: 0 AN: 32072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2706

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 901682

Other (OTH) AF: 0.00 AC: 0 AN: 39718

⚠️ 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

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.93
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.020
Sift	Benign	0.83	T
Sift4G	Benign	0.44	T
Polyphen		0.75	P
Vest4		0.29
MutPred		0.26		Gain of catalytic residue at P53 (P = 5e-04)
MVP		0.29
MPC		0.44
ClinPred		0.11	T
GERP RS		1.9
PromoterAI		0.0017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
gMVP		0.14
Mutation Taster		=89/11	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: rs1251720215; hg19: chr14-102786274;