rs367753617

Variant names:

• chr14-64951118-G-A
• rs367753617
• NM_001308154.2:c.280C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-64951118-G-A
• chr14-64951118-G-T

Variant summary

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

The NM_001308154.2(RAB15):​c.280C>T​(p.Arg94Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: RAB15 NM_001308154.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94
• Publications: 0 publications found

Genes affected

RAB15 (HGNC:20150): (RAB15, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in positive regulation of regulated secretory pathway. Located in cilium; endosome membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CHURC1-FNTB (HGNC:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308154.2. 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
	RAB15	NM_001308154.2	MANE Select	c.280C>T	p.Arg94Cys	missense	Exon 4 of 7	NP_001295083.1	G5EMR8
	RAB15	NM_198686.3		c.280C>T	p.Arg94Cys	missense	Exon 4 of 7	NP_941959.1	P59190-2
	RAB15	NM_001330182.2		c.142C>T	p.Arg48Cys	missense	Exon 5 of 8	NP_001317111.1	G3V562

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB15	ENST00000533601.7	TSL:1 MANE Select	c.280C>T	p.Arg94Cys	missense	Exon 4 of 7	ENSP00000434103.3	P59190-1
	RAB15	ENST00000267512.9	TSL:1	c.280C>T	p.Arg94Cys	missense	Exon 4 of 7	ENSP00000267512.5	P59190-2
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+25038G>A		intron	N/A	ENSP00000447121.2	B4DL54

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000360 AC: 9 AN: 249786 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000492

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1460280 Hom.: 0 Cov.: 32 AF XY: 0.0000262 AC XY: 19 AN XY: 726552

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111902

Other (OTH) AF: 0.0000497 AC: 3 AN: 60374

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74314

African (AFR) AF: 0.000266 AC: 11 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.4	L
PhyloP100		8.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.93
MPC		1.6
ClinPred		0.58	D
GERP RS		5.6
Varity_R		0.44
gMVP		0.60
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs367753617; hg19: chr14-65417836; COSMIC: COSV99962232; COSMIC: COSV99962232;