Genetic Variant GINS3:p.Ala86Asp (chr16-58395172-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001126129.2(GINS3):c.257C>A(p.Ala86Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 427,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GINS3
NM_001126129.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.945

Publications

0 publications found

Variant links:

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

GINS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017597258).

BP6

Variant 16-58395172-C-A is Benign according to our data. Variant chr16-58395172-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3036998.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126129.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GINS3	NM_022770.4	MANE Select	c.186+2385C>A		intron	N/A	NP_073607.2
GINS3	NM_001126129.2		c.257C>A	p.Ala86Asp	missense	Exon 2 of 4	NP_001119601.1	A0A0S2Z5P2
GINS3	NM_001126130.2		c.186+2385C>A		intron	N/A	NP_001119602.1	A0A0S2Z5L4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GINS3	ENST00000426538.6	TSL:1	c.257C>A	p.Ala86Asp	missense	Exon 2 of 4	ENSP00000401018.2	Q9BRX5-3
GINS3	ENST00000318129.6	TSL:1 MANE Select	c.186+2385C>A		intron	N/A	ENSP00000318196.6	Q9BRX5-1
GINS3	ENST00000328514.11	TSL:1	c.186+2385C>A		intron	N/A	ENSP00000327449.7	Q9BRX5-2

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

162

AN:

148828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000737

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00148

GnomAD2 exomes

AF:

0.00

AC:

AN:

7582

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

AN:

278130

Hom.:

Cov.:

AF XY:

0.0000970

AC XY:

AN XY:

144306

show subpopulations

African (AFR)

AF:

0.00335

AC:

AN:

7470

American (AMR)

AF:

0.000360

AC:

AN:

8336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10506

East Asian (EAS)

AF:

0.00

AC:

AN:

23178

South Asian (SAS)

AF:

0.00

AC:

AN:

9892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22780

Middle Eastern (MID)

AF:

0.000711

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

175500

Other (OTH)

AF:

0.000340

AC:

AN:

17654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00109

AC:

162

AN:

148890

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

72538

show subpopulations

African (AFR)

AF:

0.00365

AC:

148

AN:

40558

American (AMR)

AF:

0.000737

AC:

AN:

14930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67440

Other (OTH)

AF:

0.00146

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000996

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GINS3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

(source)

DANN

Benign

0.68

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.39

M_CAP

Benign

0.0011

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

PhyloP100

-0.94

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.91

REVEL

Benign

0.010

Sift

Benign

0.73

Sift4G

Benign

0.13

Vest4

0.11

MVP

0.12

MPC

0.44

ClinPred

0.022

GERP RS

0.11

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over