20-59191758-T-C

Position:

• chr20-59191758-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178457.3(ZNF831):​c.739T>C​(p.Ser247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ZNF831 NM_178457.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.547

Genes affected

ZNF831 (HGNC:16167): (zinc finger protein 831) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2529515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF831	NM_178457.3	c.739T>C	p.Ser247Pro	missense_variant	2/6	ENST00000371030.4	NP_848552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF831	ENST00000371030.4	c.739T>C	p.Ser247Pro	missense_variant	2/6	1	NM_178457.3	ENSP00000360069.2
ZNF831	ENST00000637017.1	c.739T>C	p.Ser247Pro	missense_variant	4/8	5		ENSP00000490240.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455676 Hom.: 0 Cov.: 31 AF XY: 0.00000967 AC XY: 7 AN XY: 723642

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000992

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000314 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2024

The c.739T>C (p.S247P) alteration is located in exon 1 (coding exon 1) of the ZNF831 gene. This alteration results from a T to C substitution at nucleotide position 739, causing the serine (S) at amino acid position 247 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.35	.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.073
Sift	Benign	0.050	.;D
Sift4G	Uncertain	0.032	.;D
Polyphen		1.0	D;D
Vest4		0.15
MutPred		0.20		Gain of catalytic residue at S247 (P = 0.0119);Gain of catalytic residue at S247 (P = 0.0119);
MVP		0.18
MPC		0.82
ClinPred		0.31	T
GERP RS		3.8
Varity_R		0.19
gMVP		0.40

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: rs765822206; hg19: chr20-57766813;