1-52857325-C-T

Variant names:

• chr1-52857325-C-T
• NM_001004339.3:c.584C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004339.3(ZYG11A):​c.584C>T​(p.Thr195Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: ZYG11A NM_001004339.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.617
• Publications: 0 publications found

Genes affected

ZYG11A (HGNC:32058): (zyg-11 family member A, cell cycle regulator) Predicted to be part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10382286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004339.3. 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
	ZYG11A	NM_001004339.3	MANE Select	c.584C>T	p.Thr195Ile	missense	Exon 3 of 14	NP_001004339.2	Q6WRX3-1
	ZYG11A	NM_001307931.2		c.-19+2695C>T		intron	N/A	NP_001294860.1	Q6WRX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYG11A	ENST00000371528.2	TSL:5 MANE Select	c.584C>T	p.Thr195Ile	missense	Exon 3 of 14	ENSP00000360583.1	Q6WRX3-1
	ZYG11A	ENST00000371532.5	TSL:5	c.-19+2695C>T		intron	N/A	ENSP00000360587.1	Q6WRX3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.62
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.089
Sift	Uncertain	0.022	D
Sift4G	Benign	0.095	T
Polyphen		0.13	B
Vest4		0.091
MutPred		0.49		Gain of helix (P = 0.0854)
MVP		0.085
ClinPred		0.87	D
GERP RS		-5.8
Varity_R		0.11
gMVP		0.33
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

hg19: chr1-53322997;