Variant chr20-38497507-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_020336.4(RALGAPB):c.544A>G(p.Thr182Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,455,422 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: not found (cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RALGAPB
NM_020336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94

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:

RALGAPB (HGNC:):

RALGAPB links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.30020314).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGAPB	NM_020336.4 linkuse as main transcript	c.544A>G	p.Thr182Ala	missense_variant	4/30	ENST00000262879.11	NP_065069.1	Q86X10-1Q6MZJ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGAPB	ENST00000262879.11 linkuse as main transcript	c.544A>G	p.Thr182Ala	missense_variant	4/30	1	NM_020336.4	ENSP00000262879.6		Q86X10-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243984

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

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:

0.00000900

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1455422

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000689

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Jul 26, 2022

The c.544A>G (p.T182A) alteration is located in exon 4 (coding exon 3) of the RALGAPB gene. This alteration results from a A to G substitution at nucleotide position 544, causing the threonine (T) at amino acid position 182 to be replaced by an alanine (A). 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

0.094

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;T;T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;.;D;D

M_CAP

Benign

0.0089

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

L;L;L;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.85

.;P;P;.

Vest4

0.75

MutPred

0.39

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;

MVP

0.26

MPC

0.84

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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