16-58403155-C-A

Variant names:

• chr16-58403155-C-A
• rs571698877
• NM_022770.4:c.244C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_022770.4(GINS3):​c.244C>A​(p.Arg82Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GINS3 NM_022770.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 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: 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 (BayesDel_noAF=-0.15).
• BP7: Synonymous conserved (PhyloP=2.75 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022770.4. 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
	GINS3	NM_022770.4	MANE Select	c.244C>A	p.Arg82Arg	synonymous	Exon 2 of 3	NP_073607.2
	GINS3	NM_001126129.2		c.361C>A	p.Arg121Arg	synonymous	Exon 3 of 4	NP_001119601.1	A0A0S2Z5P2
	GINS3	NM_001126130.2		c.187-1344C>A		intron	N/A	NP_001119602.1	A0A0S2Z5L4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS3	ENST00000318129.6	TSL:1 MANE Select	c.244C>A	p.Arg82Arg	synonymous	Exon 2 of 3	ENSP00000318196.6	Q9BRX5-1
	GINS3	ENST00000426538.6	TSL:1	c.361C>A	p.Arg121Arg	synonymous	Exon 3 of 4	ENSP00000401018.2	Q9BRX5-3
	GINS3	ENST00000328514.11	TSL:1	c.187-1344C>A		intron	N/A	ENSP00000327449.7	Q9BRX5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		2.7

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: rs571698877; hg19: chr16-58437059;