Variant 20-38517841-T-C 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.1258T>C(p.Ser420Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,948 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RALGAPB
NM_020336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 5.81

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:

Genome browser will be placed here

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=0.26617408).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALGAPB	NM_020336.4 linkuse as main transcript	c.1258T>C	p.Ser420Pro	missense_variant	9/30	ENST00000262879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALGAPB	ENST00000262879.11 linkuse as main transcript	c.1258T>C	p.Ser420Pro	missense_variant	9/30	1	NM_020336.4	P4	Q86X10-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727190

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:

0.00000809

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

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 22, 2024

The c.1258T>C (p.S420P) alteration is located in exon 9 (coding exon 8) of the RALGAPB gene. This alteration results from a T to C substitution at nucleotide position 1258, causing the serine (S) at amino acid position 420 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

High myopia

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;.;D;D

M_CAP

Benign

0.0079

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.4

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.13

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.085

T;T;T;D

Sift4G

Benign

0.15

T;T;T;T

Polyphen

1.0

.;D;D;D

Vest4

0.70

MutPred

0.20

Loss of phosphorylation at S420 (P = 0.0143);Loss of phosphorylation at S420 (P = 0.0143);Loss of phosphorylation at S420 (P = 0.0143);.;

MVP

0.18

MPC

1.2

ClinPred

0.77

GERP RS

5.1

Varity_R

0.17

gMVP

0.51

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