ENST00000369454:c.*282G>T

Variant names:

• chrX-155260521-C-A
• rs147213132
• NM_171998.4:c.*282G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000369454.4(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 ENST00000369454.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• early-onset parkinsonism-intellectual disability syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• intellectual disability, X-linked 72

  Inheritance: XL Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369454.4. 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
	RAB39B	NM_171998.4	MANE Select	c.*282G>T		3_prime_UTR	Exon 2 of 2	NP_741995.1	Q96DA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB39B	ENST00000369454.4	TSL:1 MANE Select	c.*282G>T		3_prime_UTR	Exon 2 of 2	ENSP00000358466.3	Q96DA2

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 786 AN: 111537 Hom.: 7 Cov.: 23

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.: 2 Cov.: 0 AF XY: 0.000789 AC XY: 58 AN XY: 73476

African (AFR) AF: 0.0263 AC: 226 AN: 8603

American (AMR) AF: 0.00143 AC: 18 AN: 12625

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8162

East Asian (EAS) AF: 0.000103 AC: 2 AN: 19404

South Asian (SAS) AF: 0.0000556 AC: 1 AN: 17975

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17009

Middle Eastern (MID) AF: 0.000906 AC: 1 AN: 1104

European-Non Finnish (NFE) AF: 0.0000759 AC: 12 AN: 158033

Other (OTH) AF: 0.00199 AC: 32 AN: 16081

GnomAD4 genome AF: 0.00708 AC: 790 AN: 111591 Hom.: 7 Cov.: 23 AF XY: 0.00577 AC XY: 195 AN XY: 33779

African (AFR) AF: 0.0242 AC: 741 AN: 30680

American (AMR) AF: 0.00265 AC: 28 AN: 10550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2641

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000170 AC: 9 AN: 53085

Other (OTH) AF: 0.00792 AC: 12 AN: 1516

Alfa AF: 0.00605 Hom.: 15

Bravo AF: 0.00879

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, X-linked 72 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs147213132; hg19: chrX-154489806;