20-59191213-C-G

Variant names:

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

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>G​(p.Thr65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,564,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• 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=0.27526295).

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>G	p.Thr65Arg	missense	Exon 2 of 6	NP_848552.1	Q5JPB2
	ZNF831	NM_001384354.1		c.194C>G	p.Thr65Arg	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>G	p.Thr65Arg	missense	Exon 2 of 6	ENSP00000360069.2	Q5JPB2
	ZNF831	ENST00000637017.1	TSL:5	c.194C>G	p.Thr65Arg	missense	Exon 4 of 8	ENSP00000490240.1	Q5JPB2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000154 AC: 3 AN: 194764 AF XY: 0.00000936

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000332

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 18 AN: 1412090 Hom.: 0 Cov.: 30 AF XY: 0.0000115 AC XY: 8 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: 0.0000165 AC: 18 AN: 1089154

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.090
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.093	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.37		Loss of loop (P = 0.0112)
MVP		0.081
MPC		0.85
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.22
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;