8-41536413-T-G

Variant names:

• chr8-41536413-T-G
• rs778406591
• NM_032336.3:c.150T>G

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.150T>G​(p.Ile50Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GINS4 NM_032336.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.143
• 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=0.14784545).

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.150T>G	p.Ile50Met	missense	Exon 3 of 8	NP_115712.1	Q9BRT9-1
	GPAT4-AS1	NR_125824.1		n.303+658A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS4	ENST00000276533.4	TSL:1 MANE Select	c.150T>G	p.Ile50Met	missense	Exon 3 of 8	ENSP00000276533.3	Q9BRT9-1
	GINS4	ENST00000518671.5	TSL:3	c.150T>G	p.Ile50Met	missense	Exon 3 of 8	ENSP00000428754.1	Q9BRT9-1
	GINS4	ENST00000523277.6	TSL:5	c.150T>G	p.Ile50Met	missense	Exon 3 of 7	ENSP00000428901.1	E5RFF9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251378 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1459080 Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11 AN XY: 726090

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1109490

Other (OTH) AF: 0.0000166 AC: 1 AN: 60282

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.14
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.054
Sift	Benign	0.054	T
Sift4G	Benign	0.36	T
Polyphen		0.11	B
Vest4		0.46
MutPred		0.58		Gain of ubiquitination at K47 (P = 0.0467)
MVP		0.16
MPC		0.46
ClinPred		0.033	T
GERP RS		-1.2
Varity_R		0.11
gMVP		0.24
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs778406591; hg19: chr8-41393932;