NM_018335.6:c.221A>C

Variant names:

• chr14-102319986-A-C
• NM_018335.6:c.221A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018335.6(ZNF839):​c.221A>C​(p.Gln74Pro) 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. 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: 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: 1.88
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30829954).

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.221A>C	p.Gln74Pro	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.221A>C	p.Gln74Pro	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.221A>C	p.Gln74Pro	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.221A>C	p.Gln74Pro	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.221A>C	p.Gln74Pro	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.221A>C	p.Gln74Pro	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1021440 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 484806

African (AFR) AF: 0.00 AC: 0 AN: 20456

American (AMR) AF: 0.00 AC: 0 AN: 6266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11194

East Asian (EAS) AF: 0.00 AC: 0 AN: 20550

South Asian (SAS) AF: 0.00 AC: 0 AN: 18926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 885540

Other (OTH) AF: 0.00 AC: 0 AN: 38740

GnomAD4 genome Cov.: 32

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	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.89
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.089
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.20		Loss of MoRF binding (P = 0.0839)
MVP		0.46
MPC		0.45
ClinPred		0.82	D
GERP RS		1.4
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.36
Mutation Taster		=76/24	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

hg19: chr14-102786323;