rs1365622597

Variant names:

• chr1-52771451-C-G
• rs1365622597
• NM_024646.3:c.628C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-52771451-C-G
• chr1-52771451-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024646.3(ZYG11B):​c.628C>G​(p.Arg210Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZYG11B NM_024646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 1 publications found

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]

ZYG11B Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42352968).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024646.3. 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
	ZYG11B	NM_024646.3	MANE Select	c.628C>G	p.Arg210Gly	missense	Exon 3 of 14	NP_078922.1	Q9C0D3-1
	ZYG11B	NM_001441954.1		c.616C>G	p.Arg206Gly	missense	Exon 4 of 15	NP_001428883.1
	ZYG11B	NR_199864.1		n.829C>G		non_coding_transcript_exon	Exon 3 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYG11B	ENST00000294353.7	TSL:1 MANE Select	c.628C>G	p.Arg210Gly	missense	Exon 3 of 14	ENSP00000294353.6	Q9C0D3-1
	ZYG11B	ENST00000884648.1		c.625C>G	p.Arg209Gly	missense	Exon 3 of 14	ENSP00000554707.1
	ZYG11B	ENST00000959293.1		c.628C>G	p.Arg210Gly	missense	Exon 3 of 13	ENSP00000629352.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250784 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461300 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726952

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111828

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.031
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.17	T
Polyphen		0.037	B
Vest4		0.65
MutPred		0.54		Loss of stability (P = 0.0464)
MVP		0.15
MPC		1.2
ClinPred		0.69	D
GERP RS		3.2
Varity_R		0.74
gMVP		0.59
Mutation Taster		=58/42	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

dbSNP: rs1365622597; hg19: chr1-53237123;