14-102319971-T-G

Position:

• chr14-102319971-T-G

Variant summary

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

The NM_018335.6(ZNF839):​c.206T>G​(p.Leu69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000982 in 1,018,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.755

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF839	NM_018335.6	c.206T>G	p.Leu69Arg	missense_variant	1/8	ENST00000442396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF839	ENST00000442396.7	c.206T>G	p.Leu69Arg	missense_variant	1/8	5	NM_018335.6	A2
ZNF839	ENST00000558850.5	c.-61+2305T>G		intron_variant		2		P2
ZNF839	ENST00000559185.5	c.-61+453T>G		intron_variant		2		P2
ZNF839	ENST00000559098.5	c.14T>G	p.Leu5Arg	missense_variant, NMD_transcript_variant	1/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.82e-7 AC: 1 AN: 1018220 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 486212

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: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2022

The c.206T>G (p.L69R) alteration is located in exon 1 (coding exon 1) of the ZNF839 gene. This alteration results from a T to G substitution at nucleotide position 206, causing the leucine (L) at amino acid position 69 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.35		Loss of stability (P = 0.0369);
MVP		0.51
MPC		0.55
ClinPred		0.99	D
GERP RS		2.5
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-102786308;