16-85678584-C-G

Variant names:

• chr16-85678584-C-G
• rs187043080
• NM_016095.3:c.388G>C

Variant summary

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

The NM_016095.3(GINS2):​c.388G>C​(p.Val130Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. V130M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GINS2 NM_016095.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44
• Publications: 0 publications found

Genes affected

GINS2 (HGNC:24575): (GINS complex subunit 2) The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1 (GINS1; MIM 610608), Psf2, and Psf3 (GINS3; MIM 610610). The formation of this 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]

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=0.20696488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016095.3. 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
	GINS2	NM_016095.3	MANE Select	c.388G>C	p.Val130Leu	missense	Exon 4 of 5	NP_057179.1	Q9Y248

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS2	ENST00000253462.8	TSL:1 MANE Select	c.388G>C	p.Val130Leu	missense	Exon 4 of 5	ENSP00000253462.3	Q9Y248
	GINS2	ENST00000919083.1		c.403G>C	p.Val135Leu	missense	Exon 4 of 5	ENSP00000589142.1
	GINS2	ENST00000595355.5	TSL:3	c.193G>C	p.Val65Leu	missense	Exon 4 of 4	ENSP00000470984.1	M0R043

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.64	N
PhyloP100		4.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.097
Sift	Benign	0.22	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.42		Gain of catalytic residue at V130 (P = 0.0214)
MVP		0.30
MPC		0.0080
ClinPred		0.68	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.39

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: rs187043080; hg19: chr16-85712190;