16-31435954-C-T

Variant names:

• chr16-31435954-C-T
• rs563212163
• NM_001136509.3:c.896G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136509.3(ZNF843):​c.896G>A​(p.Arg299Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R299T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF843 NM_001136509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 0 publications found

Genes affected

ZNF843 (HGNC:28710): (zinc finger protein 843) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11528611).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136509.3. 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
	ZNF843	NM_001136509.3	MANE Select	c.896G>A	p.Arg299Lys	missense	Exon 2 of 2	NP_001129981.1	Q8N446
	ZNF843	NM_001353381.1		c.896G>A	p.Arg299Lys	missense	Exon 2 of 2	NP_001340310.1	Q8N446

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF843	ENST00000315678.10	TSL:2 MANE Select	c.896G>A	p.Arg299Lys	missense	Exon 2 of 2	ENSP00000322899.5	Q8N446
	ZNF843	ENST00000618063.1	TSL:1	c.896G>A	p.Arg299Lys	missense	Exon 2 of 2	ENSP00000483573.1	Q8N446
	ZNF843	ENST00000857608.1		c.896G>A	p.Arg299Lys	missense	Exon 2 of 2	ENSP00000527667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386288 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682708

African (AFR) AF: 0.00 AC: 0 AN: 31298

American (AMR) AF: 0.00 AC: 0 AN: 34174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24242

East Asian (EAS) AF: 0.00 AC: 0 AN: 35606

South Asian (SAS) AF: 0.00 AC: 0 AN: 77414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072610

Other (OTH) AF: 0.00 AC: 0 AN: 57402

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.4
DANN	Benign	0.56
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.28
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.77	T
Polyphen		0.86	P
Vest4		0.061
MutPred		0.17		Gain of ubiquitination at R299 (P = 0.0082)
MVP		0.014
ClinPred		0.14	T
GERP RS		0.37
Varity_R		0.077
gMVP		0.028

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: rs563212163; hg19: chr16-31447275;