rs747867822

Variant names:

• chr14-64951121-C-G
• rs747867822
• NM_001308154.2:c.277G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64951121-C-G
• chr14-64951121-C-T

Variant summary

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

The NM_001308154.2(RAB15):​c.277G>C​(p.Glu93Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,448 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E93K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB15 NM_001308154.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• Publications: 2 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.277G>C	p.Glu93Gln	missense	Exon 4 of 7	NP_001295083.1	G5EMR8
	RAB15	NM_198686.3		c.277G>C	p.Glu93Gln	missense	Exon 4 of 7	NP_941959.1	P59190-2
	RAB15	NM_001330182.2		c.139G>C	p.Glu47Gln	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.277G>C	p.Glu93Gln	missense	Exon 4 of 7	ENSP00000434103.3	P59190-1
	RAB15	ENST00000267512.9	TSL:1	c.277G>C	p.Glu93Gln	missense	Exon 4 of 7	ENSP00000267512.5	P59190-2
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+25041C>G		intron	N/A	ENSP00000447121.2	B4DL54

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249870 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460448 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726630

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52062

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.30	N
PhyloP100		7.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.43
Sift	Benign	0.47	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.34		Gain of MoRF binding (P = 0.0462)
MVP		0.90
MPC		0.86
ClinPred		0.66	D
GERP RS		5.6
Varity_R		0.34
gMVP		0.46
Mutation Taster		=13/87	disease causing

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: rs747867822; hg19: chr14-65417839;