2-106413126-G-C

Variant names:

• chr2-106413126-G-C
• NM_001144013.2:c.5224C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144013.2(RGPD3):​c.5224C>G​(p.Leu1742Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70
• Publications: 0 publications found

Genes affected

RGPD3 (HGNC:32416): (RANBP2 like and GRIP domain containing 3) This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain. [provided by RefSeq, Sep 2011]

ENSG00000291125 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3014078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD3	NM_001144013.2	c.5224C>G	p.Leu1742Val	missense_variant	Exon 22 of 23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2	c.5248C>G	p.Leu1750Val	missense_variant	Exon 23 of 24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4	c.5224C>G	p.Leu1742Val	missense_variant	Exon 22 of 23	1	NM_001144013.2	ENSP00000386588.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5224C>G (p.L1742V) alteration is located in exon 22 (coding exon 22) of the RGPD3 gene. This alteration results from a C to G substitution at nucleotide position 5224, causing the leucine (L) at amino acid position 1742 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0038	.;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.7	.;M
PhyloP100		5.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.44	.;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.99	.;D
Vest4		0.51
MutPred		0.66		.;Loss of disorder (P = 0.1879);
MVP		0.15
ClinPred		0.76	D
GERP RS		1.1
Varity_R		0.19
gMVP		0.081
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-107029582;