rs376381703

Variant names:

• chr8-41539751-C-A
• NM_032336.3:c.371C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-41539751-C-A
• chr8-41539751-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032336.3(GINS4):​c.371C>A​(p.Pro124Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GINS4 NM_032336.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GINS4	NM_032336.3	c.371C>A	p.Pro124Gln	missense_variant	Exon 5 of 8	ENST00000276533.4	NP_115712.1
GINS4	XM_005273659.5	c.371C>A	p.Pro124Gln	missense_variant	Exon 5 of 8		XP_005273716.1
GPAT4-AS1	NR_125824.1	n.64-2441G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINS4	ENST00000276533.4	c.371C>A	p.Pro124Gln	missense_variant	Exon 5 of 8	1	NM_032336.3	ENSP00000276533.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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	Benign	0.099
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;.;T
M_CAP	Benign	0.0082	T
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.068	T;T;T
Polyphen		0.97	D;D;.
Vest4		0.69
MutPred		0.47		Loss of glycosylation at P124 (P = 0.0207);Loss of glycosylation at P124 (P = 0.0207);Loss of glycosylation at P124 (P = 0.0207);
MVP		0.67
MPC		0.27
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-41397270; COSMIC: COSV104583404; COSMIC: COSV104583404;