14-102319950-T-A

Position:

• chr14-102319950-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018335.6(ZNF839):​c.185T>A​(p.Leu62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3026362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF839	NM_018335.6	c.185T>A	p.Leu62Gln	missense_variant	1/8	ENST00000442396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF839	ENST00000442396.7	c.185T>A	p.Leu62Gln	missense_variant	1/8	5	NM_018335.6	A2
ZNF839	ENST00000558850.5	c.-61+2284T>A		intron_variant		2		P2
ZNF839	ENST00000559185.5	c.-61+432T>A		intron_variant		2		P2
ZNF839	ENST00000559098.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1019958 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 489294

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: 0.00

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

Dec 07, 2021

The c.185T>A (p.L62Q) alteration is located in exon 1 (coding exon 1) of the ZNF839 gene. This alteration results from a T to A substitution at nucleotide position 185, causing the leucine (L) at amino acid position 62 to be replaced by a glutamine (Q). 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	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Benign	0.95
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.22		Gain of catalytic residue at P58 (P = 0.002);
MVP		0.53
MPC		0.45
ClinPred		0.85	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.17

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: chr14-102786287;