20-25407872-G-CA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021067.5(GINS1):c.52delinsCA(p.Glu18GlnfsTer24) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GINS1 NM_021067.5 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.96

Genes affected

GINS1 (HGNC:28980): (GINS complex subunit 1) The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1, Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]).[supplied by OMIM, Mar 2008]

LOC105372581 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GINS1	NM_021067.5	c.52delinsCA	p.Glu18GlnfsTer24	frameshift_variant	1/7	ENST00000262460.5
LOC105372581	XR_937403.3	n.225+199delinsTG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GINS1	ENST00000262460.5	c.52delinsCA	p.Glu18GlnfsTer24	frameshift_variant	1/7	1	NM_021067.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Combined immunodeficiency due to GINS1 deficiency Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Clinical Genomics Program, Stanford Medicine

Aug 30, 2019

The p.Glu18Glnfs*24 variant in the GINS1 gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Glu18Glnfs*24 variant causes a shift in the protein reading frame, leading to a premature termination codon 24 amino acids downstream. It is currently unknown if GINS1 loss of function is associated with disease. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Glu18Glnfs*24 variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2] -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2090256422; hg19: chr20-25388508;