rs8054945

Variant names:

• chr16-58401134-G-A
• rs8054945
• NM_022770.4:c.187-1964G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022770.4(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 NM_022770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 2 publications found

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]

GINS3 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GINS3	NM_022770.4	c.187-1964G>A		intron_variant	Intron 1 of 2	ENST00000318129.6	NP_073607.2
GINS3	NM_001126129.2	c.304-1964G>A		intron_variant	Intron 2 of 3		NP_001119601.1
GINS3	NM_001126130.2	c.187-3365G>A		intron_variant	Intron 1 of 1		NP_001119602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINS3	ENST00000318129.6	c.187-1964G>A		intron_variant	Intron 1 of 2	1	NM_022770.4	ENSP00000318196.6
GINS3	ENST00000426538.6	c.304-1964G>A		intron_variant	Intron 2 of 3	1		ENSP00000401018.2
GINS3	ENST00000328514.11	c.187-3365G>A		intron_variant	Intron 1 of 1	1		ENSP00000327449.7

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

African (AFR) AF: 0.0729 AC: 3022 AN: 41458

American (AMR) AF: 0.0416 AC: 636 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3468

East Asian (EAS) AF: 0.0126 AC: 65 AN: 5176

South Asian (SAS) AF: 0.0246 AC: 118 AN: 4798

European-Finnish (FIN) AF: 0.0172 AC: 182 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3135 AN: 67958

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0472 Hom.: 23

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
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs8054945; hg19: chr16-58435038;