Variant X-155260521-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_171998.4(RAB39B):c.*282G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 370,587 control chromosomes in the GnomAD database, including 9 homozygotes. There are 253 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 7 hom., 195 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 2 hom. 58 hem. )

Consequence

RAB39B
NM_171998.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.360

Variant links:

Genes affected

RAB39B (HGNC:16499): (RAB39B, member RAS oncogene family) This gene encodes a member of the Rab family of proteins. Rab proteins are small GTPases that are involved in vesicular trafficking. Mutations in this gene are associated with X-linked cognitive disability. [provided by RefSeq, Aug 2013]

RAB39B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-155260521-C-A is Benign according to our data. Variant chrX-155260521-C-A is described in ClinVar as [Benign]. Clinvar id is 368144.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00708 (790/111591) while in subpopulation AFR AF= 0.0242 (741/30680). AF 95% confidence interval is 0.0227. There are 7 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB39B	NM_171998.4 linkuse as main transcript	c.*282G>T		3_prime_UTR_variant	2/2	ENST00000369454.4	NP_741995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB39B	ENST00000369454.4 linkuse as main transcript	c.*282G>T		3_prime_UTR_variant	2/2	1	NM_171998.4	ENSP00000358466	P1

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

786

AN:

111537

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

193

AN XY:

33715

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00266

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:

0.000170

Gnomad OTH

AF:

0.00802

GnomAD4 exome

AF:

0.00113

AC:

292

AN:

258996

Hom.:

Cov.:

AF XY:

0.000789

AC XY:

AN XY:

73476

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.0000556

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000759

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00708

AC:

790

AN:

111591

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

195

AN XY:

33779

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000170

Gnomad4 OTH

AF:

0.00792

Alfa

AF:

0.00605

Hom.:

Bravo

AF:

0.00879

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 72

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.6

DANN

Benign

0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over