rs891701812

Variant names:

• chr14-102319796-G-A
• rs891701812
• NM_018335.6:c.31G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-102319796-G-A
• chr14-102319796-G-C
• chr14-102319796-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018335.6(ZNF839):​c.31G>A​(p.Gly11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,080,344 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055809736).

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.31G>A	p.Gly11Ser	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.31G>A	p.Gly11Ser	missense	Exon 1 of 7	NP_001371994.1
	ZNF839	NM_001385072.1		c.31G>A	p.Gly11Ser	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.31G>A	p.Gly11Ser	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.31G>A	p.Gly11Ser	missense	Exon 1 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.31G>A	p.Gly11Ser	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000278 AC: 30 AN: 1080344 Hom.: 0 Cov.: 30 AF XY: 0.0000235 AC XY: 12 AN XY: 511176

African (AFR) AF: 0.00 AC: 0 AN: 22782

American (AMR) AF: 0.00 AC: 0 AN: 8308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14246

East Asian (EAS) AF: 0.00 AC: 0 AN: 26372

South Asian (SAS) AF: 0.00 AC: 0 AN: 20400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3064

European-Non Finnish (NFE) AF: 0.0000326 AC: 30 AN: 920482

Other (OTH) AF: 0.00 AC: 0 AN: 43554

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.88
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.021
Sift	Benign	0.52	T
Sift4G	Benign	0.49	T
Polyphen		0.36	B
Vest4		0.17
MutPred		0.14		Gain of phosphorylation at G11 (P = 0.0045)
MVP		0.040
MPC		0.084
ClinPred		0.19	T
GERP RS		1.0
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
gMVP		0.14
Mutation Taster		=99/1	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: rs891701812; hg19: chr14-102786133;