NM_001136509.3:c.949G>T

Variant names:

• chr16-31435901-C-A
• rs2082177291
• NM_001136509.3:c.949G>T

Variant summary

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

The NM_001136509.3(ZNF843):​c.949G>T​(p.Ala317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,392,056 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ZNF843 NM_001136509.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -8.43
• 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: 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=0.04823935).

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.949G>T	p.Ala317Ser	missense	Exon 2 of 2	NP_001129981.1	Q8N446
	ZNF843	NM_001353381.1		c.949G>T	p.Ala317Ser	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.949G>T	p.Ala317Ser	missense	Exon 2 of 2	ENSP00000322899.5	Q8N446
	ZNF843	ENST00000618063.1	TSL:1	c.949G>T	p.Ala317Ser	missense	Exon 2 of 2	ENSP00000483573.1	Q8N446
	ZNF843	ENST00000857608.1		c.949G>T	p.Ala317Ser	missense	Exon 2 of 2	ENSP00000527667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1392056 Hom.: 0 Cov.: 30 AF XY: 0.00000583 AC XY: 4 AN XY: 686082

African (AFR) AF: 0.00 AC: 0 AN: 31420

American (AMR) AF: 0.00 AC: 0 AN: 34960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24758

East Asian (EAS) AF: 0.00 AC: 0 AN: 35628

South Asian (SAS) AF: 0.0000639 AC: 5 AN: 78290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075606

Other (OTH) AF: 0.00 AC: 0 AN: 57688

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	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.2
DANN	Benign	0.80
DEOGEN2	Benign	0.00084	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-8.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.29	T
Polyphen		0.058	B
Vest4		0.077
MutPred		0.093		Gain of glycosylation at A317 (P = 0.0105)
MVP		0.014
ClinPred		0.085	T
GERP RS		-4.3
Varity_R		0.091
gMVP		0.0090
Mutation Taster		=100/0	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: rs2082177291; hg19: chr16-31447222;