NM_022337.3:c.483+12489T>C

Variant names:

• chr11-88137186-A-G
• rs12270038
• NM_022337.3:c.483+12489T>C

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+12489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,040 control chromosomes in the GnomAD database, including 14,191 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 0.43 (14191 hom., cov: 32)
• Consequence: RAB38 NM_022337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB38	NM_022337.3	c.483+12489T>C		intron_variant	Intron 2 of 2	ENST00000243662.11	NP_071732.1
RAB38	XM_017017455.3	c.483+12489T>C		intron_variant	Intron 2 of 3		XP_016872944.1
RAB38	XM_017017456.3	c.483+12489T>C		intron_variant	Intron 2 of 3		XP_016872945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB38	ENST00000243662.11	c.483+12489T>C		intron_variant	Intron 2 of 2	1	NM_022337.3	ENSP00000243662.5
RAB38	ENST00000526372.1	c.477+12489T>C		intron_variant	Intron 2 of 2	3		ENSP00000433317.1
RAB38	ENST00000531138.1	c.251-23046T>C		intron_variant	Intron 1 of 1	2		ENSP00000435340.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65492 AN: 151922 Hom.: 14170 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.431 AC: 65560 AN: 152040 Hom.: 14191 Cov.: 32 AF XY: 0.432 AC XY: 32113 AN XY: 74300

African (AFR) AF: 0.430 AC: 17859 AN: 41486

American (AMR) AF: 0.401 AC: 6125 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3464

East Asian (EAS) AF: 0.305 AC: 1578 AN: 5168

South Asian (SAS) AF: 0.435 AC: 2095 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4974 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29765 AN: 67964

Other (OTH) AF: 0.448 AC: 947 AN: 2114

Alfa AF: 0.445 Hom.: 1971

Bravo AF: 0.421

Asia WGS AF: 0.402 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.79
PhyloP100		-0.18
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: rs12270038; hg19: chr11-87870354;