8-41539774-G-C

Variant names:

• chr8-41539774-G-C
• rs1806804302
• NM_032336.3:c.394G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032336.3(GINS4):​c.394G>C​(p.Glu132Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. E132K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GINS4 NM_032336.3 missense, splice_region
• Scores: Splicing: ADA: 0.0001205
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24950081).

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.394G>C	p.Glu132Gln	missense splice_region	Exon 5 of 8	NP_115712.1	Q9BRT9-1
	GPAT4-AS1	NR_125824.1		n.64-2464C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS4	ENST00000276533.4	TSL:1 MANE Select	c.394G>C	p.Glu132Gln	missense splice_region	Exon 5 of 8	ENSP00000276533.3	Q9BRT9-1
	GINS4	ENST00000518671.5	TSL:3	c.394G>C	p.Glu132Gln	missense splice_region	Exon 5 of 8	ENSP00000428754.1	Q9BRT9-1
	GINS4	ENST00000523277.6	TSL:5	c.394G>C	p.Glu132Gln	missense splice_region	Exon 5 of 7	ENSP00000428901.1	E5RFF9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.046	D
Sift4G	Uncertain	0.041	D
Polyphen		0.27	B
Vest4		0.39
MutPred		0.55		Loss of disorder (P = 0.0977)
MVP		0.52
MPC		0.26
ClinPred		0.82	D
GERP RS		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.34
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0040
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: rs1806804302; hg19: chr8-41397293;