11-61898354-G-C

Variant names:

• chr11-61898354-G-C
• rs977026851
• NM_013401.4:c.1073C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013401.4(RAB3IL1):​c.1073C>G​(p.Pro358Arg) 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. P358L) 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: 3.34
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23941341).

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.1073C>G	p.Pro358Arg	missense	Exon 10 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.995C>G	p.Pro332Arg	missense	Exon 9 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.1073C>G	p.Pro358Arg	missense	Exon 10 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.995C>G	p.Pro332Arg	missense	Exon 9 of 9	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.1358C>G	p.Pro453Arg	missense	Exon 11 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.0015
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.064
Sift	Benign	0.051	T
Sift4G	Benign	0.12	T
Polyphen		0.45	P
Vest4		0.24
MutPred		0.35		Gain of MoRF binding (P = 4e-04)
MVP		0.66
MPC		0.16
ClinPred		0.80	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.41
Mutation Taster		=75/25	polymorphism

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: rs977026851; hg19: chr11-61665826;