rs756048663

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-61902515-C-A
• chr11-61902515-C-T
• chr11-61902515-C-G

Variant summary

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

The NM_013401.4(RAB3IL1):​c.926G>T​(p.Arg309Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000812 in 1,601,736 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. R309H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84
• Publications: 2 publications found

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

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_013401.4. 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
	RAB3IL1	NM_013401.4	MANE Select	c.926G>T	p.Arg309Leu	missense	Exon 8 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.848G>T	p.Arg283Leu	missense	Exon 7 of 9	NP_001258615.1	Q8TBN0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3IL1	ENST00000394836.7	TSL:1 MANE Select	c.926G>T	p.Arg309Leu	missense	Exon 8 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.848G>T	p.Arg283Leu	missense	Exon 7 of 9	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.1211G>T	p.Arg404Leu	missense	Exon 9 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226494 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000828 AC: 12 AN: 1449578 Hom.: 0 Cov.: 31 AF XY: 0.00000973 AC XY: 7 AN XY: 719748

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 41962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39176

South Asian (SAS) AF: 0.00 AC: 0 AN: 83280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1108040

Other (OTH) AF: 0.0000500 AC: 3 AN: 59952

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000165 Hom.: 0

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	0.16
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.8
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.17
Sift	Benign	0.051	T
Sift4G	Uncertain	0.055	T
Polyphen		0.66	P
Vest4		0.71
MutPred		0.54		Loss of MoRF binding (P = 0.0012)
MVP		0.69
MPC		0.15
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.38
gMVP		0.77
Mutation Taster		=31/69	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: rs756048663; hg19: chr11-61669987;