16-31435901-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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: 0.0000043 (0 hom.)
• Consequence: ZNF843 NM_001136509.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -8.43

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04823935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF843	NM_001136509.3	c.949G>T	p.Ala317Ser	missense_variant	Exon 2 of 2	ENST00000315678.10	NP_001129981.1
ZNF843	NM_001353381.1	c.949G>T	p.Ala317Ser	missense_variant	Exon 2 of 2		NP_001340310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF843	ENST00000315678.10	c.949G>T	p.Ala317Ser	missense_variant	Exon 2 of 2	2	NM_001136509.3	ENSP00000322899.5
ZNF843	ENST00000618063.1	c.949G>T	p.Ala317Ser	missense_variant	Exon 2 of 2	1		ENSP00000483573.1
ZNF843	ENST00000564218.5	c.682+267G>T		intron_variant	Intron 2 of 2	5		ENSP00000455858.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000639

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.949G>T (p.A317S) alteration is located in exon 2 (coding exon 1) of the ZNF843 gene. This alteration results from a G to T substitution at nucleotide position 949, causing the alanine (A) at amino acid position 317 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.020	N;.
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.29	T;T
Polyphen		0.058	B;B
Vest4		0.077
MutPred		0.093		Gain of glycosylation at A317 (P = 0.0105);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2082177291; hg19: chr16-31447222;