rs782356686

Variant names:

• chrX-154442440-G-A
• rs782356686
• NM_001493.3:c.1191+12G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-154442440-G-A
• chrX-154442440-G-C
• chrX-154442440-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001493.3(GDI1):​c.1191+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,208,742 control chromosomes in the GnomAD database, including 1 homozygotes. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.000085 (1 hom. 26 hem.)
• Consequence: GDI1 NM_001493.3 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.129
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000259 (29/112043) while in subpopulation AMR AF = 0.00215 (23/10684). AF 95% confidence interval is 0.00147. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDI1	NM_001493.3	c.1191+12G>A		intron_variant	Intron 10 of 10	ENST00000447750.7	NP_001484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDI1	ENST00000447750.7	c.1191+12G>A		intron_variant	Intron 10 of 10	1	NM_001493.3	ENSP00000394071.2

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 29 AN: 111988 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

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: 0.00266

GnomAD2 exomes AF: 0.000202 AC: 37 AN: 183443 AF XY: 0.000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000721

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000848 AC: 93 AN: 1096699 Hom.: 1 Cov.: 31 AF XY: 0.0000718 AC XY: 26 AN XY: 362077

African (AFR) AF: 0.00 AC: 0 AN: 26370

American (AMR) AF: 0.00207 AC: 73 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.000199 AC: 6 AN: 30202

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54117

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840764

Other (OTH) AF: 0.000239 AC: 11 AN: 46042

GnomAD4 genome AF: 0.000259 AC: 29 AN: 112043 Hom.: 0 Cov.: 23 AF XY: 0.000292 AC XY: 10 AN XY: 34239

African (AFR) AF: 0.0000648 AC: 2 AN: 30879

American (AMR) AF: 0.00215 AC: 23 AN: 10684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3535

South Asian (SAS) AF: 0.00 AC: 0 AN: 2717

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6097

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53061

Other (OTH) AF: 0.00262 AC: 4 AN: 1525

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000548

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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: rs782356686; hg19: chrX-153670787;