chr8-41542007-C-G

Variant names:

• chr8-41542007-C-G
• rs1055455430
• NM_032336.3:c.592C>G

Variant summary

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

The NM_032336.3(GINS4):​c.592C>G​(p.Leu198Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GINS4 NM_032336.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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)

ENSG00000253174 (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 rank	MANE	Protein	UniProt
GINS4	NM_032336.3	c.592C>G	p.Leu198Val	missense_variant	Exon 8 of 8	ENST00000276533.4	NP_115712.1
GINS4	XM_005273659.5	c.592C>G	p.Leu198Val	missense_variant	Exon 8 of 8		XP_005273716.1
GPAT4-AS1	NR_125824.1	n.64-4697G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINS4	ENST00000276533.4	c.592C>G	p.Leu198Val	missense_variant	Exon 8 of 8	1	NM_032336.3	ENSP00000276533.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250540 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135528

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	0.028
Eigen_PC	Benign	0.0073
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.069	T;T
Polyphen		0.87	P;P
Vest4		0.58
MutPred		0.66		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.52
MPC		0.33
ClinPred		0.73	D
GERP RS		-0.36
Varity_R		0.43
gMVP		0.58

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: rs1055455430; hg19: chr8-41399526;