20-59191213-C-A

Variant names:

• chr20-59191213-C-A
• rs778876349
• NM_178457.3:c.194C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178457.3(ZNF831):​c.194C>A​(p.Thr65Lys) 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. 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. T65M) has been classified 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: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30144882).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178457.3. 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
	ZNF831	NM_178457.3	MANE Select	c.194C>A	p.Thr65Lys	missense	Exon 2 of 6	NP_848552.1	Q5JPB2
	ZNF831	NM_001384354.1		c.194C>A	p.Thr65Lys	missense	Exon 4 of 8	NP_001371283.1	Q5JPB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF831	ENST00000371030.4	TSL:1 MANE Select	c.194C>A	p.Thr65Lys	missense	Exon 2 of 6	ENSP00000360069.2	Q5JPB2
	ZNF831	ENST00000637017.1	TSL:5	c.194C>A	p.Thr65Lys	missense	Exon 4 of 8	ENSP00000490240.1	Q5JPB2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1412090 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698244

African (AFR) AF: 0.00 AC: 0 AN: 32066

American (AMR) AF: 0.00 AC: 0 AN: 38092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39216

South Asian (SAS) AF: 0.00 AC: 0 AN: 79328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089154

Other (OTH) AF: 0.00 AC: 0 AN: 58248

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.045
Eigen_PC	Benign	0.052
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.41		Gain of methylation at T65 (P = 0.0122)
MVP		0.081
MPC		0.88
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.42
Mutation Taster		=94/6	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: rs778876349; hg19: chr20-57766268;