11-88143743-T-C

Variant names:

• chr11-88143743-T-C
• rs302668
• NM_022337.3:c.483+5932A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022337.3(RAB38):​c.483+5932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,116 control chromosomes in the GnomAD database, including 6,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6572 hom., cov: 32)
• Consequence: RAB38 NM_022337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 12 publications found

Genes affected

RAB38 (HGNC:9776): (RAB38, member RAS oncogene family) Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB38	NM_022337.3	MANE Select	c.483+5932A>G		intron	N/A	NP_071732.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB38	ENST00000243662.11	TSL:1 MANE Select	c.483+5932A>G		intron	N/A	ENSP00000243662.5
	RAB38	ENST00000916357.1		c.483+5932A>G		intron	N/A	ENSP00000586416.1
	RAB38	ENST00000526372.1	TSL:3	c.477+5932A>G		intron	N/A	ENSP00000433317.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42339 AN: 151998 Hom.: 6566 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42366 AN: 152116 Hom.: 6572 Cov.: 32 AF XY: 0.282 AC XY: 20960 AN XY: 74352

African (AFR) AF: 0.140 AC: 5812 AN: 41502

American (AMR) AF: 0.317 AC: 4857 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1566 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4814

European-Finnish (FIN) AF: 0.376 AC: 3969 AN: 10560

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22640 AN: 67976

Other (OTH) AF: 0.316 AC: 669 AN: 2116

Alfa AF: 0.314 Hom.: 3536

Bravo AF: 0.264

Asia WGS AF: 0.309 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.055
DANN	Benign	0.48
PhyloP100		-1.1
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: rs302668; hg19: chr11-87876911;