chr14-102320049-C-T

Variant names:

• chr14-102320049-C-T
• rs922158545
• NM_018335.6:c.284C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018335.6(ZNF839):​c.284C>T​(p.Pro95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,182,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P95S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2307893).

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.284C>T	p.Pro95Leu	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.284C>T	p.Pro95Leu	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.284C>T	p.Pro95Leu	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.284C>T	p.Pro95Leu	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.284C>T	p.Pro95Leu	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.284C>T	p.Pro95Leu	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 151820 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 4 AF XY: 0.00

Gnomad FIN exome AF: 0.00

GnomAD4 exome AF: 0.000285 AC: 294 AN: 1030286 Hom.: 0 Cov.: 30 AF XY: 0.000257 AC XY: 125 AN XY: 485976

African (AFR) AF: 0.0000951 AC: 2 AN: 21026

American (AMR) AF: 0.000444 AC: 3 AN: 6762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12030

East Asian (EAS) AF: 0.00 AC: 0 AN: 22774

South Asian (SAS) AF: 0.000924 AC: 17 AN: 18398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18264

Middle Eastern (MID) AF: 0.00262 AC: 7 AN: 2674

European-Non Finnish (NFE) AF: 0.000287 AC: 255 AN: 888396

Other (OTH) AF: 0.000250 AC: 10 AN: 39962

GnomAD4 genome AF: 0.000224 AC: 34 AN: 151930 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74256

African (AFR) AF: 0.000169 AC: 7 AN: 41528

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67888

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000212

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	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.0046
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.15
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.070
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.21		Loss of sheet (P = 0.0084)
MVP		0.37
MPC		0.30
ClinPred		0.96	D
GERP RS		2.3
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
gMVP		0.11
Mutation Taster		=85/15	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: rs922158545; hg19: chr14-102786386;