NM_024646.3:c.857C>T

Variant names:

• chr1-52771680-C-T
• rs756327281
• NM_024646.3:c.857C>T

Variant summary

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

The NM_024646.3(ZYG11B):​c.857C>T​(p.Ala286Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A286D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZYG11B NM_024646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

Genes affected

ZYG11B (HGNC:25820): (zyg-11 family member B, cell cycle regulator) Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and protein quality control for misfolded or incompletely synthesized proteins. Part of Cul2-RING ubiquitin ligase complex. [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=0.2353454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.857C>T	p.Ala286Val	missense_variant	Exon 3 of 14	ENST00000294353.7	NP_078922.1
ZYG11B	XM_006710898.5	c.845C>T	p.Ala282Val	missense_variant	Exon 3 of 14		XP_006710961.1
ZYG11B	XM_017002336.3	c.857C>T	p.Ala286Val	missense_variant	Exon 3 of 11		XP_016857825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7	c.857C>T	p.Ala286Val	missense_variant	Exon 3 of 14	1	NM_024646.3	ENSP00000294353.6
ZYG11B	ENST00000545132.5	c.857C>T	p.Ala286Val	missense_variant	Exon 3 of 14	2		ENSP00000441315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	.;T
Eigen	Benign	0.099
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.14
Sift	Benign	0.29	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.018	.;B
Vest4		0.48
MutPred		0.27		Loss of ubiquitination at K282 (P = 0.0699);Loss of ubiquitination at K282 (P = 0.0699);
MVP		0.043
MPC		0.97
ClinPred		0.68	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.50

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: rs756327281; hg19: chr1-53237352;