11-61902515-C-G

Variant names:

• chr11-61902515-C-G
• rs756048663
• NM_013401.4:c.926G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013401.4(RAB3IL1):​c.926G>C​(p.Arg309Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,578 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. R309H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84

Genes affected

RAB3IL1 (HGNC:9780): (RAB3A interacting protein like 1) This gene encodes a guanine nucleotide exchange factor for the ras-related protein Rab3A. The encoded protein binds Rab3a and the inositol hexakisphosphate kinase InsP6K1. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3IL1	NM_013401.4	c.926G>C	p.Arg309Pro	missense_variant	Exon 8 of 10	ENST00000394836.7	NP_037533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3IL1	ENST00000394836.7	c.926G>C	p.Arg309Pro	missense_variant	Exon 8 of 10	1	NM_013401.4	ENSP00000378313.2
RAB3IL1	ENST00000301773.9	c.848G>C	p.Arg283Pro	missense_variant	Exon 7 of 9	1		ENSP00000301773.5
RAB3IL1	ENST00000531922.2	c.1211G>C	p.Arg404Pro	missense_variant	Exon 9 of 11	3		ENSP00000435444.2
RAB3IL1	ENST00000530888.1	n.184G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449578 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.96	D;P
Vest4		0.77
MutPred		0.50		Loss of MoRF binding (P = 4e-04);.;
MVP		0.74
MPC		0.38
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.70
gMVP		0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs756048663; hg19: chr11-61669987; COSMIC: COSV57117687; COSMIC: COSV57117687;