11-61906519-C-G

Variant names:

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

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>C​(p.Ala202Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. A202D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.05092606).

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>C	p.Ala202Pro	missense	Exon 5 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.579+874G>C		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>C	p.Ala202Pro	missense	Exon 5 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.579+874G>C		intron	N/A	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.745G>C	p.Ala249Pro	missense	Exon 5 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000606 AC: 1 AN: 164926 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: 0.0000150

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.94
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.042
Sift	Benign	0.47	T
Sift4G	Benign	0.46	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.24		Gain of glycosylation at A202 (P = 0.0416)
MVP		0.29
MPC		0.11
ClinPred		0.046	T
GERP RS		0.82
Varity_R		0.044
gMVP		0.24
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;