chr16-58401134-G-A

Position:

• chr16-58401134-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000318129.6(GINS3):​c.187-1964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,054 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.048 (188 hom., cov: 31)
• Consequence: GINS3 ENST00000318129.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

Genes affected

GINS3 (HGNC:25851): (GINS complex subunit 3) This gene encodes a protein subunit of the GINS heterotetrameric complex, which is essential for the initiation of DNA replication and replisome progression in eukaryotes. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GINS3	NM_022770.4	c.187-1964G>A		intron_variant		ENST00000318129.6	NP_073607.2
GINS3	NM_001126129.2	c.304-1964G>A		intron_variant			NP_001119601.1
GINS3	NM_001126130.2	c.187-3365G>A		intron_variant			NP_001119602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GINS3	ENST00000318129.6	c.187-1964G>A		intron_variant		1	NM_022770.4	ENSP00000318196	P1
GINS3	ENST00000328514.11	c.187-3365G>A		intron_variant		1		ENSP00000327449
GINS3	ENST00000426538.6	c.304-1964G>A		intron_variant		1		ENSP00000401018

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7297 AN: 151936 Hom.: 188 Cov.: 31

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0480 AC: 7300 AN: 152054 Hom.: 188 Cov.: 31 AF XY: 0.0464 AC XY: 3451 AN XY: 74340

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.0246

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0464 Hom.: 21

Bravo AF: 0.0498

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.94

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: rs8054945; hg19: chr16-58435038;