rs554301

Variant names:

• chr1-52856276-A-T
• rs554301
• NM_001004339.3:c.257-722A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004339.3(ZYG11A):​c.257-722A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,758 control chromosomes in the GnomAD database, including 18,305 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (18305 hom., cov: 30)
• Consequence: ZYG11A NM_001004339.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYG11A	NM_001004339.3	c.257-722A>T		intron_variant	Intron 2 of 13	ENST00000371528.2	NP_001004339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYG11A	ENST00000371528.2	c.257-722A>T		intron_variant	Intron 2 of 13	5	NM_001004339.3	ENSP00000360583.1
ZYG11A	ENST00000371532.5	c.-19+1646A>T		intron_variant	Intron 2 of 12	5		ENSP00000360587.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71657 AN: 151640 Hom.: 18316 Cov.: 30

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.472 AC: 71639 AN: 151758 Hom.: 18305 Cov.: 30 AF XY: 0.463 AC XY: 34355 AN XY: 74148

African (AFR) AF: 0.349 AC: 14444 AN: 41376

American (AMR) AF: 0.393 AC: 5967 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1706 AN: 3462

East Asian (EAS) AF: 0.0269 AC: 139 AN: 5174

South Asian (SAS) AF: 0.512 AC: 2463 AN: 4810

European-Finnish (FIN) AF: 0.513 AC: 5395 AN: 10510

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39942 AN: 67908

Other (OTH) AF: 0.478 AC: 1010 AN: 2114

Alfa AF: 0.531 Hom.: 2781

Bravo AF: 0.453

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs554301; hg19: chr1-53321948; COSMIC: COSV65292552;