NM_013401.4:c.1073C>T

Variant names:

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

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>T​(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,052 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RAB3IL1 NM_013401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.15378872).

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>T	p.Pro358Leu	missense	Exon 10 of 10	NP_037533.2
	RAB3IL1	NM_001271686.2		c.995C>T	p.Pro332Leu	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>T	p.Pro358Leu	missense	Exon 10 of 10	ENSP00000378313.2	Q8TBN0-1
	RAB3IL1	ENST00000301773.9	TSL:1	c.995C>T	p.Pro332Leu	missense	Exon 9 of 9	ENSP00000301773.5	Q8TBN0-2
	RAB3IL1	ENST00000531922.2	TSL:3	c.1358C>T	p.Pro453Leu	missense	Exon 11 of 11	ENSP00000435444.2	E9PK89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461052 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726822

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 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	0.085
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.048
Sift	Benign	0.058	T
Sift4G	Benign	0.094	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.35		Gain of helix (P = 0.0128)
MVP		0.53
MPC		0.086
ClinPred		0.70	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.42
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;