chr11-61906519-C-T

Variant names:

• chr11-61906519-C-T
• rs774752186
• NM_013401.4:c.604G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013401.4(RAB3IL1):​c.604G>A​(p.Ala202Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,555,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A202D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.944
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037370384).

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.604G>A	p.Ala202Thr	missense	Exon 5 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.579+874G>A		intron	N/A	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.604G>A	p.Ala202Thr	missense	Exon 5 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.579+874G>A		intron	N/A	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.745G>A	p.Ala249Thr	missense	Exon 5 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000424 AC: 7 AN: 164926 AF XY: 0.0000569

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: 0.000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000620 AC: 87 AN: 1403812 Hom.: 0 Cov.: 31 AF XY: 0.0000721 AC XY: 50 AN XY: 693450

African (AFR) AF: 0.00 AC: 0 AN: 32168

American (AMR) AF: 0.00 AC: 0 AN: 36452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.0000544 AC: 2 AN: 36786

South Asian (SAS) AF: 0.00 AC: 0 AN: 80036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4360

European-Non Finnish (NFE) AF: 0.0000738 AC: 80 AN: 1083588

Other (OTH) AF: 0.0000859 AC: 5 AN: 58208

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152002 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74236

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15258

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000122 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000425 AC: 5

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	0.064
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.7
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.94
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.041
Sift	Benign	0.26	T
Sift4G	Benign	0.59	T
Polyphen		0.0040	B
Vest4		0.095
MVP		0.19
MPC		0.082
ClinPred		0.024	T
GERP RS		0.82
Varity_R		0.031
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs774752186; hg19: chr11-61673991;