Variant 20-38509147-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_020336.4(RALGAPB):c.811C>G(p.Pro271Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RALGAPB
NM_020336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

RALGAPB (HGNC:29221): (Ral GTPase activating protein non-catalytic subunit beta) Enables protein heterodimerization activity. Predicted to be involved in activation of GTPase activity. Predicted to act upstream of or within Ral protein signal transduction; regulation of exocyst localization; and regulation of protein localization. [provided by Alliance of Genome Resources, Apr 2022]

RALGAPB links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RALGAPB. . Gene score misZ 3.1771 (greater than the threshold 3.09). Trascript score misZ 4.2843 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALGAPB	NM_020336.4 linkuse as main transcript	c.811C>G	p.Pro271Ala	missense_variant	6/30	ENST00000262879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALGAPB	ENST00000262879.11 linkuse as main transcript	c.811C>G	p.Pro271Ala	missense_variant	6/30	1	NM_020336.4	P4	Q86X10-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461136

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726950

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RALGAPB-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 26, 2023

The RALGAPB c.811C>G variant is predicted to result in the amino acid substitution p.Pro271Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.6

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.8

D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.018

D;D;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.83

.;P;P;.

Vest4

0.63

MutPred

0.36

Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);.;

MVP

0.18

MPC

1.3

ClinPred

0.98

GERP RS

5.3

Varity_R

0.30

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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