NM_024646.3:c.956C>T

Variant names:

• chr1-52779857-C-T
• rs189751502
• NM_024646.3:c.956C>T

Variant summary

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

The NM_024646.3(ZYG11B):​c.956C>T​(p.Ser319Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S319C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZYG11B NM_024646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11B	NM_024646.3	c.956C>T	p.Ser319Phe	missense_variant	Exon 4 of 14	ENST00000294353.7	NP_078922.1
ZYG11B	XM_006710898.5	c.944C>T	p.Ser315Phe	missense_variant	Exon 4 of 14		XP_006710961.1
ZYG11B	XM_017002336.3	c.956C>T	p.Ser319Phe	missense_variant	Exon 4 of 11		XP_016857825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11B	ENST00000294353.7	c.956C>T	p.Ser319Phe	missense_variant	Exon 4 of 14	1	NM_024646.3	ENSP00000294353.6
ZYG11B	ENST00000545132.5	c.956C>T	p.Ser319Phe	missense_variant	Exon 4 of 14	2		ENSP00000441315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.98	.;D
Vest4		0.78
MutPred		0.42		Loss of disorder (P = 0.0048);Loss of disorder (P = 0.0048);
MVP		0.043
MPC		2.0
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.55
gMVP		0.62

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: rs189751502; hg19: chr1-53245529;