15-55224004-G-T

Variant names:

• chr15-55224004-G-T
• rs104894500
• NM_183235.3:c.352C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_183235.3(RAB27A):​c.352C>A​(p.Gln118Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RAB27A NM_183235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.88

Genes affected

RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30423757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.352C>A	p.Gln118Lys	missense_variant	Exon 6 of 7	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.352C>A	p.Gln118Lys	missense_variant	Exon 6 of 7	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251234 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135786

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 7.02e-7 AC: 1 AN: 1424198 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 710294

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Benign	0.66
DEOGEN2	Benign	0.27	T;T;T;T;T;.;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;.;.;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.040	N;N;N;N;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.11	N;N;N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	0.95	T;T;T;T;.;.;T
Polyphen		0.058	B;B;B;B;.;.;.
Vest4		0.86
MutPred		0.45		Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);
MVP		0.51
MPC		0.15
ClinPred		0.54	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs104894500; hg19: chr15-55516202;