chr1-52842971-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001004339.3(ZYG11A):​c.88C>T​(p.Gln30*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ZYG11A NM_001004339.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.9662
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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>T	p.Gln30*	stop_gained splice_region	Exon 1 of 14	NP_001004339.2	Q6WRX3-1
	ZYG11A	NM_001307931.2		c.-187C>T		splice_region	Exon 1 of 13	NP_001294860.1	Q6WRX3-2
	ZYG11A	NM_001307931.2		c.-187C>T		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>T	p.Gln30*	stop_gained splice_region	Exon 1 of 14	ENSP00000360583.1	Q6WRX3-1
	ZYG11A	ENST00000371532.5	TSL:5	c.-187C>T		splice_region	Exon 1 of 13	ENSP00000360587.1	Q6WRX3-2
	ZYG11A	ENST00000371532.5	TSL:5	c.-187C>T		5_prime_UTR	Exon 1 of 13	ENSP00000360587.1	Q6WRX3-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364478 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 672836

African (AFR) AF: 0.00 AC: 0 AN: 27776

American (AMR) AF: 0.00 AC: 0 AN: 30410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24168

East Asian (EAS) AF: 0.00 AC: 0 AN: 30670

South Asian (SAS) AF: 0.00 AC: 0 AN: 75474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065140

Other (OTH) AF: 0.00 AC: 0 AN: 56528

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	44
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.66	D
PhyloP100		0.77
Vest4		0.064
GERP RS		4.0
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=44/156	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.73
SpliceAI score (max)		0.010		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;