20-38535152-G-T

Variant names:

• chr20-38535152-G-T
• rs758022116
• NM_020336.4:c.2324G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_020336.4(RALGAPB):​c.2324G>T​(p.Arg775Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALGAPB NM_020336.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-38535152-G-T is Pathogenic according to our data. Variant chr20-38535152-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 370037.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALGAPB	NM_020336.4	c.2324G>T	p.Arg775Leu	missense_variant	Exon 16 of 30	ENST00000262879.11	NP_065069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALGAPB	ENST00000262879.11	c.2324G>T	p.Arg775Leu	missense_variant	Exon 16 of 30	1	NM_020336.4	ENSP00000262879.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251422 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135888

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Septo-optic dysplasia sequence Pathogenic:1

Oct 06, 2016

Shaikh Laboratory, University of Colorado

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.8	.;L;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.99, 0.86	.;D;D;P
Vest4		0.75
MutPred		0.34		.;Loss of MoRF binding (P = 0.0157);Loss of MoRF binding (P = 0.0157);.;
MVP		0.28
MPC		1.3
ClinPred		0.94	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.37
gMVP		0.59

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

Other links and lift over

dbSNP: rs758022116; hg19: chr20-37163795;