1-52842950-G-C

Position:

• chr1-52842950-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004339.3(ZYG11A):​c.67G>C​(p.Ala23Pro) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZYG11A NM_001004339.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057498544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYG11A	NM_001004339.3	c.67G>C	p.Ala23Pro	missense_variant	1/14	ENST00000371528.2	NP_001004339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYG11A	ENST00000371528.2	c.67G>C	p.Ala23Pro	missense_variant	1/14	5	NM_001004339.3	ENSP00000360583	P1
ZYG11A	ENST00000371532.5	c.-208G>C		5_prime_UTR_variant	1/13	5		ENSP00000360587

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.67G>C (p.A23P) alteration is located in exon 1 (coding exon 1) of the ZYG11A gene. This alteration results from a G to C substitution at nucleotide position 67, causing the alanine (A) at amino acid position 23 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.00058	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.063
Sift	Benign	0.15	T
Sift4G	Benign	0.24	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.34		Gain of disorder (P = 0.0774);
MVP		0.030
ClinPred		0.050	T
GERP RS		3.2
Varity_R		0.13
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051056584; hg19: chr1-53308622;