1-52842971-C-G

Variant names:

• chr1-52842971-C-G
• rs1347347925
• NM_001004339.3:c.88C>G

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.88C>G​(p.Gln30Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ZYG11A NM_001004339.3 missense, splice_region
• Scores: Splicing: ADA: 0.1659
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.767
• 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=0.10367498).

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.88C>G	p.Gln30Glu	missense splice_region	Exon 1 of 14	NP_001004339.2	Q6WRX3-1
	ZYG11A	NM_001307931.2		c.-187C>G		splice_region	Exon 1 of 13	NP_001294860.1	Q6WRX3-2
	ZYG11A	NM_001307931.2		c.-187C>G		5_prime_UTR	Exon 1 of 13	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.88C>G	p.Gln30Glu	missense splice_region	Exon 1 of 14	ENSP00000360583.1	Q6WRX3-1
	ZYG11A	ENST00000371532.5	TSL:5	c.-187C>G		splice_region	Exon 1 of 13	ENSP00000360587.1	Q6WRX3-2
	ZYG11A	ENST00000371532.5	TSL:5	c.-187C>G		5_prime_UTR	Exon 1 of 13	ENSP00000360587.1	Q6WRX3-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.063
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.77
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.064
Sift	Benign	0.066	T
Sift4G	Benign	0.50	T
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.41		Loss of helix (P = 0.028)
MVP		0.014
ClinPred		0.32	T
GERP RS		4.0
PromoterAI		0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.31
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.17
dbscSNV1_RF	Benign	0.33
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: rs1347347925; hg19: chr1-53308643;