Variant 1-174272448-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366446.1(RABGAP1L):c.1021G>A(p.Val341Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,600,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RABGAP1L
NM_001366446.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.79

Variant links:

Genes affected

RABGAP1L (HGNC:24663): (RAB GTPase activating protein 1 like) Enables GTPase activator activity and small GTPase binding activity. Acts upstream of or within regulation of protein localization. Located in Golgi apparatus; early endosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RABGAP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1 linkuse as main transcript	c.1021G>A	p.Val341Met	missense_variant	8/26	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1 linkuse as main transcript	c.1021G>A	p.Val341Met	missense_variant	8/26		NM_001366446.1	ENSP00000507884	P2
RABGAP1L	ENST00000357444.10 linkuse as main transcript	c.910G>A	p.Val304Met	missense_variant	8/14	1		ENSP00000350027		Q5R372-2
RABGAP1L	ENST00000457696.1 linkuse as main transcript	c.1057G>A	p.Val353Met	missense_variant	8/13	1		ENSP00000403136
RABGAP1L	ENST00000251507.8 linkuse as main transcript	c.1021G>A	p.Val341Met	missense_variant	8/21	2		ENSP00000251507	A1	Q5R372-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240538

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130532

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1448934

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

720520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151850

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.1021G>A (p.V341M) alteration is located in exon 1 (coding exon 1) of the RABGAP1L gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the valine (V) at amino acid position 341 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Uncertain

-0.033

MutationAssessor

Uncertain

2.7

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

N;N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.72

MutPred

0.45

.;Loss of methylation at K342 (P = 0.0308);.;

MVP

0.78

MPC

0.91

ClinPred

0.97

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.39

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over