20-59191305-C-T

Variant names:

• chr20-59191305-C-T
• rs374647671
• NM_178457.3:c.286C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178457.3(ZNF831):​c.286C>T​(p.Gln96*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000694 in 1,440,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF831 NM_178457.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• 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 2 ACMG points.

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

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.286C>T	p.Gln96*	stop_gained	Exon 2 of 6	NP_848552.1	Q5JPB2
	ZNF831	NM_001384354.1		c.286C>T	p.Gln96*	stop_gained	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.286C>T	p.Gln96*	stop_gained	Exon 2 of 6	ENSP00000360069.2	Q5JPB2
	ZNF831	ENST00000637017.1	TSL:5	c.286C>T	p.Gln96*	stop_gained	Exon 4 of 8	ENSP00000490240.1	Q5JPB2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440410 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714994

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.00 AC: 0 AN: 41882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 38686

South Asian (SAS) AF: 0.00 AC: 0 AN: 84124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101738

Other (OTH) AF: 0.0000168 AC: 1 AN: 59420

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.87	D
PhyloP100		3.7
Vest4		0.057
GERP RS		4.7
Mutation Taster		=22/178	disease causing (fs/PTC)

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: rs374647671; hg19: chr20-57766360;