8-41537252-CGC-GGA

Variant names:

• chr8-41537252-CGC-GGA
• NM_032336.3:c.256_258delCGCinsGGA
• GINS4 p.Arg86Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_032336.3(GINS4):​c.256_258delCGCinsGGA​(p.Arg86Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R86C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GINS4 NM_032336.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

Genes affected

GINS4 (HGNC:28226): (GINS complex subunit 4) The yeast heterotetrameric GINS complex is made up of Sld5, Psf1 (GINS1; MIM 610608), 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]). See GINS1 for additional information about the GINS complex.[supplied by OMIM, Mar 2008]

GPAT4-AS1 (HGNC:55539): (GPAT4 and GINS4 antisense RNA 1)

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032336.3. 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
	GINS4	NM_032336.3	MANE Select	c.256_258delCGCinsGGA	p.Arg86Gly	missense	N/A	NP_115712.1	Q9BRT9-1
	GPAT4-AS1	NR_125824.1		n.120_122delGCGinsTCC		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS4	ENST00000276533.4	TSL:1 MANE Select	c.256_258delCGCinsGGA	p.Arg86Gly	missense	N/A	ENSP00000276533.3	Q9BRT9-1
	GINS4	ENST00000518671.5	TSL:3	c.256_258delCGCinsGGA	p.Arg86Gly	missense	N/A	ENSP00000428754.1	Q9BRT9-1
	GINS4	ENST00000523277.6	TSL:5	c.256_258delCGCinsGGA	p.Arg86Gly	missense	N/A	ENSP00000428901.1	E5RFF9

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

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: chr8-41394771;