rs143418001

chrX-155264196-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_171998.4(RAB39B):c.93T>C(p.Gly31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,210,496 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 0.00021 (0 hom., 6 hem., cov: 24)
  • Exomes 𝑓: 0.000015 (0 hom. 5 hem.)
• Consequence: RAB39B NM_171998.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant X-155264196-A-G is Benign according to our data. Variant chrX-155264196-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 436460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.379 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB39B	NM_171998.4	c.93T>C	p.Gly31=	synonymous_variant	1/2	ENST00000369454.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB39B	ENST00000369454.4	c.93T>C	p.Gly31=	synonymous_variant	1/2	1	NM_171998.4	P1

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 23 AN: 112394 Hom.: 0 Cov.: 24 AF XY: 0.000145 AC XY: 5 AN XY: 34580

Gnomad AFR AF: 0.000582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000373

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: 0.000654

GnomAD3 exomes AF: 0.0000491 AC: 9 AN: 183454 Hom.: 0 AF XY: 0.0000589 AC XY: 4 AN XY: 67894

Gnomad AFR exome AF: 0.000532

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.0000146 AC: 16 AN: 1098049 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 363405

Gnomad4 AFR exome AF: 0.000417

Gnomad4 AMR exome AF: 0.0000852

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome AF: 0.000213 AC: 24 AN: 112447 Hom.: 0 Cov.: 24 AF XY: 0.000173 AC XY: 6 AN XY: 34643

Gnomad4 AFR AF: 0.000613

Gnomad4 AMR AF: 0.000372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000646

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000374

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 22, 2016

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs143418001; hg19: chrX-154493481;