dbSNP rs988932047: GDI1:p.Ile8Ile (chrX-154437278-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001493.3(GDI1):c.24C>A(p.Ile8Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,121 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GDI1
NM_001493.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

GDI1 (HGNC:4226): (GDP dissociation inhibitor 1) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed primarily in neural and sensory tissues. Mutations in GDI1 have been linked to X-linked nonspecific cognitive disability. [provided by RefSeq, Jul 2008]

GDI1 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 41
Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

GDI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant X-154437278-C-A is Benign according to our data. Variant chrX-154437278-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3385283.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001493.3. 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
	GDI1	NM_001493.3	MANE Select	c.24C>A	p.Ile8Ile	synonymous	Exon 1 of 11	NP_001484.1	A0A0S2Z3X8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDI1	ENST00000447750.7	TSL:1 MANE Select	c.24C>A	p.Ile8Ile	synonymous	Exon 1 of 11	ENSP00000394071.2	P31150
GDI1	ENST00000481304.5	TSL:1	n.90C>A		non_coding_transcript_exon	Exon 1 of 5
GDI1	ENST00000905223.1		c.24C>A	p.Ile8Ile	synonymous	Exon 1 of 11	ENSP00000575282.1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112121

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1093246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359782

African (AFR)

AF:

0.00

AC:

AN:

25967

American (AMR)

AF:

0.00

AC:

AN:

35099

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19261

East Asian (EAS)

AF:

0.00

AC:

AN:

29920

South Asian (SAS)

AF:

0.00

AC:

AN:

53960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39875

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4111

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839158

Other (OTH)

AF:

0.00

AC:

AN:

45895

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112121

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34317

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30879

American (AMR)

AF:

0.00

AC:

AN:

10776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3511

South Asian (SAS)

AF:

0.00

AC:

AN:

2762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53008

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.0

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over