20-25418154-GTC-ATA

Variant names:

• chr20-25418154-GTC-ATA
• NM_021067.5:c.289_291delGTCinsATA
• GINS1 p.Val97Ile

Variant summary

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

The NM_021067.5(GINS1):​c.289_291delGTCinsATA​(p.Val97Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. V97V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GINS1 NM_021067.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84
• Publications: 0 publications found

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]

GINS1 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to GINS1 deficiency

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021067.5. 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
	GINS1	NM_021067.5	MANE Select	c.289_291delGTCinsATA	p.Val97Ile	missense	N/A	NP_066545.3
	GINS1	NM_001410830.1		c.289_291delGTCinsATA	p.Val97Ile	missense	N/A	NP_001397759.1	A0A8Q3WLL7
	GINS1	NM_001410831.1		c.76-7057_76-7055delGTCinsATA		intron	N/A	NP_001397760.1	A0A8Q3WLJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	ENST00000262460.5	TSL:1 MANE Select	c.289_291delGTCinsATA	p.Val97Ile	missense	N/A	ENSP00000262460.4	Q14691
	GINS1	ENST00000696814.1		c.289_291delGTCinsATA	p.Val97Ile	missense	N/A	ENSP00000512895.1	A0A8Q3WMM5
	GINS1	ENST00000696894.1		c.289_291delGTCinsATA	p.Val97Ile	missense	N/A	ENSP00000512956.1	A0A8Q3SJ10

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-25398790;