8-41537205-G-A

Variant names:

• chr8-41537205-G-A
• rs1806755981
• NM_032336.3:c.209G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032336.3(GINS4):​c.209G>A​(p.Arg70Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,236 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 Likely benign (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: GINS4 NM_032336.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017876506).
• BP6: Variant 8-41537205-G-A is Benign according to our data. Variant chr8-41537205-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3520208.Status of the report is criteria_provided_single_submitter, 1 stars.

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.209G>A	p.Arg70Lys	missense	Exon 4 of 8	NP_115712.1	Q9BRT9-1
	GPAT4-AS1	NR_125824.1		n.169C>T		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.209G>A	p.Arg70Lys	missense	Exon 4 of 8	ENSP00000276533.3	Q9BRT9-1
	GINS4	ENST00000518671.5	TSL:3	c.209G>A	p.Arg70Lys	missense	Exon 4 of 8	ENSP00000428754.1	Q9BRT9-1
	GINS4	ENST00000523277.6	TSL:5	c.209G>A	p.Arg70Lys	missense	Exon 4 of 7	ENSP00000428901.1	E5RFF9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.057
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.34		Gain of ubiquitination at R70 (P = 0.0267)
MVP		0.40
MPC		0.26
ClinPred		0.39	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.12
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1806755981; hg19: chr8-41394724;