1-52771373-T-A

Variant names:

• chr1-52771373-T-A
• NM_024646.3:c.550T>A

Variant summary

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

The NM_024646.3(ZYG11B):​c.550T>A​(p.Ser184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZYG11B NM_024646.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

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=0.1439654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.550T>A	p.Ser184Thr	missense_variant	Exon 3 of 14	ENST00000294353.7	NP_078922.1
ZYG11B	XM_006710898.5	c.538T>A	p.Ser180Thr	missense_variant	Exon 3 of 14		XP_006710961.1
ZYG11B	XM_017002336.3	c.550T>A	p.Ser184Thr	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.550T>A	p.Ser184Thr	missense_variant	Exon 3 of 14	1	NM_024646.3	ENSP00000294353.6
ZYG11B	ENST00000545132.5	c.550T>A	p.Ser184Thr	missense_variant	Exon 3 of 14	2		ENSP00000441315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550T>A (p.S184T) alteration is located in exon 3 (coding exon 3) of the ZYG11B gene. This alteration results from a T to A substitution at nucleotide position 550, causing the serine (S) at amino acid position 184 to be replaced by a threonine (T). 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	Benign	0.075
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.047	.;T
Eigen	Benign	0.016
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.41	.;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.089
Sift	Benign	0.83	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.048	.;B
Vest4		0.34
MutPred		0.23		Loss of phosphorylation at S184 (P = 0.0644);Loss of phosphorylation at S184 (P = 0.0644);
MVP		0.068
MPC		0.87
ClinPred		0.34	T
GERP RS		5.0
Varity_R		0.10
gMVP		0.23

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: chr1-53237045;