11-88114047-C-G

Variant names:

• chr11-88114047-C-G
• rs371255484
• NM_022337.3:c.577G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022337.3(RAB38):​c.577G>C​(p.Val193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V193M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RAB38 NM_022337.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863
• Publications: 4 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]

ENSG00000255241 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1426523).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB38	NM_022337.3	MANE Select	c.577G>C	p.Val193Leu	missense	Exon 3 of 3	NP_071732.1	P57729

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB38	ENST00000243662.11	TSL:1 MANE Select	c.577G>C	p.Val193Leu	missense	Exon 3 of 3	ENSP00000243662.5	P57729
	RAB38	ENST00000916357.1		c.607G>C	p.Val203Leu	missense	Exon 4 of 4	ENSP00000586416.1
	RAB38	ENST00000526372.1	TSL:3	c.571G>C	p.Val191Leu	missense	Exon 3 of 3	ENSP00000433317.1	H0YDB7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.86
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.070	N
REVEL	Uncertain	0.34
Sift	Benign	0.25	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.32		Gain of catalytic residue at V193 (P = 0.0155)
MVP		0.84
MPC		0.072
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.10
gMVP		0.38
Mutation Taster		=80/20	polymorphism

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: rs371255484; hg19: chr11-87847215;