20-59191192-T-C

Variant summary

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

The NM_178457.3(ZNF831):c.173T>C(p.Leu58Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF831 NM_178457.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF831	NM_178457.3	c.173T>C	p.Leu58Pro	missense_variant	2/6	ENST00000371030.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF831	ENST00000371030.4	c.173T>C	p.Leu58Pro	missense_variant	2/6	1	NM_178457.3	P1
ZNF831	ENST00000637017.1	c.173T>C	p.Leu58Pro	missense_variant	4/8	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440862 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716496

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 21, 2022

The c.173T>C (p.L58P) 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 173, causing the leucine (L) at amino acid position 58 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
Polyphen		1.0	D;D
Vest4		0.53
MutPred		0.55		Gain of disorder (P = 0.0078);Gain of disorder (P = 0.0078);
MVP		0.23
MPC		1.0
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.63
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-57766247;