16-31436168-T-G

Variant names:

• chr16-31436168-T-G
• rs1198914914
• NM_001136509.3:c.682A>C

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.682A>C​(p.Ser228Arg) 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. 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. S228C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF843 NM_001136509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• 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=0.07400647).

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.682A>C	p.Ser228Arg	missense	Exon 2 of 2	NP_001129981.1	Q8N446
	ZNF843	NM_001353381.1		c.682A>C	p.Ser228Arg	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.682A>C	p.Ser228Arg	missense	Exon 2 of 2	ENSP00000322899.5	Q8N446
	ZNF843	ENST00000618063.1	TSL:1	c.682A>C	p.Ser228Arg	missense	Exon 2 of 2	ENSP00000483573.1	Q8N446
	ZNF843	ENST00000857608.1		c.682A>C	p.Ser228Arg	missense	Exon 2 of 2	ENSP00000527667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000706 AC: 1 AN: 141552 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000938

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.48
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.049	D
Polyphen		0.69	P
Vest4		0.17
MutPred		0.23		Loss of glycosylation at S228 (P = 0.0066)
MVP		0.030
ClinPred		0.093	T
GERP RS		-2.2
Varity_R		0.14
gMVP		0.24

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: rs1198914914; hg19: chr16-31447489;