Variant chr9-126965887-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_014636.3(RALGPS1):c.101A>G(p.Tyr34Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

RALGPS1
NM_014636.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

RALGPS1 (HGNC:16851): (Ral GEF with PH domain and SH3 binding motif 1) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Ral protein signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RALGPS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, RALGPS1

BP4

Computational evidence support a benign effect (MetaRNN=0.16516834).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALGPS1	NM_014636.3 linkuse as main transcript	c.101A>G	p.Tyr34Cys	missense_variant	3/19	ENST00000259351.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALGPS1	ENST00000259351.10 linkuse as main transcript	c.101A>G	p.Tyr34Cys	missense_variant	3/19	1	NM_014636.3	P1	Q5JS13-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

251044

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135654

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:

0.0000706

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000540

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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 04, 2024

The c.101A>G (p.Y34C) alteration is located in exon 3 (coding exon 2) of the RALGPS1 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the tyrosine (Y) at amino acid position 34 to be replaced by a cysteine (C). 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

Benign

0.061

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Benign

0.17

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;L;.;L;L

MutationTaster

Benign

0.99

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;N;N;D;D;N;N

REVEL

Benign

0.080

Sift

Benign

0.051

T;T;T;D;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T;T

Polyphen

0.96, 0.025, 0.92

.;D;B;.;.;.;P

Vest4

0.47

MVP

0.19

MPC

0.94

ClinPred

0.23

GERP RS

5.5

Varity_R

0.18

gMVP

0.55

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

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