rs13077101

Variant names:

• chr3-120706484-T-C
• rs13077101
• NM_173825.5:c.269-370A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173825.5(RABL3):​c.269-370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 150,704 control chromosomes in the GnomAD database, including 5,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5460 hom., cov: 30)
• Consequence: RABL3 NM_173825.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 10 publications found

Genes affected

RABL3 (HGNC:18072): (RAB, member of RAS oncogene family like 3) Predicted to enable GTP binding activity; GTPase activity; and protein homodimerization activity. Involved in regulation of Ras protein signal transduction and regulation of protein lipidation. Predicted to be active in endomembrane system. Implicated in pancreatic cancer. [provided by Alliance of Genome Resources, Apr 2022]

RABL3 Gene-Disease associations (from GenCC):

• familial pancreatic carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pancreatic cancer, susceptibility to, 5

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173825.5. 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
	RABL3	NM_173825.5	MANE Select	c.269-370A>G		intron	N/A	NP_776186.2
	RABL3	NM_001363965.1		c.269-370A>G		intron	N/A	NP_001350894.1
	RABL3	NM_001363964.1		c.269-370A>G		intron	N/A	NP_001350893.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL3	ENST00000273375.8	TSL:1 MANE Select	c.269-370A>G		intron	N/A	ENSP00000273375.4
	RABL3	ENST00000880051.1		c.269-370A>G		intron	N/A	ENSP00000550110.1
	RABL3	ENST00000880049.1		c.269-370A>G		intron	N/A	ENSP00000550108.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37168 AN: 150590 Hom.: 5463 Cov.: 30

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37165 AN: 150704 Hom.: 5460 Cov.: 30 AF XY: 0.241 AC XY: 17737 AN XY: 73532

African (AFR) AF: 0.130 AC: 5367 AN: 41358

American (AMR) AF: 0.217 AC: 3270 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1273 AN: 3434

East Asian (EAS) AF: 0.0177 AC: 92 AN: 5184

South Asian (SAS) AF: 0.322 AC: 1532 AN: 4756

European-Finnish (FIN) AF: 0.234 AC: 2416 AN: 10340

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22139 AN: 67278

Other (OTH) AF: 0.288 AC: 597 AN: 2072

Alfa AF: 0.296 Hom.: 12174

Bravo AF: 0.241

Asia WGS AF: 0.190 AC: 662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.75
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs13077101; hg19: chr3-120425331;