NM_013401.4:c.614C>G

Variant names:

• chr11-61906509-G-C
• rs150107094
• NM_013401.4:c.614C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013401.4(RAB3IL1):​c.614C>G​(p.Pro205Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000741 in 1,552,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P205S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03650132).

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.614C>G	p.Pro205Arg	missense	Exon 5 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.579+884C>G		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.614C>G	p.Pro205Arg	missense	Exon 5 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.579+884C>G		intron	N/A	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.755C>G	p.Pro252Arg	missense	Exon 5 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000559 AC: 9 AN: 160970 AF XY: 0.0000819

Gnomad AFR exome AF: 0.000853

Gnomad AMR exome AF: 0.0000396

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000400 AC: 56 AN: 1400722 Hom.: 0 Cov.: 31 AF XY: 0.0000419 AC XY: 29 AN XY: 691672

African (AFR) AF: 0.00125 AC: 40 AN: 32040

American (AMR) AF: 0.0000553 AC: 2 AN: 36172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 36552

South Asian (SAS) AF: 0.00 AC: 0 AN: 79820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46456

Middle Eastern (MID) AF: 0.000236 AC: 1 AN: 4246

European-Non Finnish (NFE) AF: 0.00000832 AC: 9 AN: 1082178

Other (OTH) AF: 0.0000689 AC: 4 AN: 58086

GnomAD4 genome AF: 0.000388 AC: 59 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33 AN XY: 74378

African (AFR) AF: 0.00132 AC: 55 AN: 41516

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67978

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000186 Hom.: 0

Bravo AF: 0.000416

ESP6500AA AF: 0.00139 AC: 6

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.0000688 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.061
Sift	Benign	0.23	T
Sift4G	Uncertain	0.055	T
Polyphen		0.055	B
Vest4		0.18
MVP		0.67
MPC		0.091
ClinPred		0.040	T
GERP RS		3.8
Varity_R		0.063
gMVP		0.38
Mutation Taster		=86/14	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: rs150107094; hg19: chr11-61673981;