2-106415860-T-C

Variant names:

• chr2-106415860-T-C
• NM_001144013.2:c.5054A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144013.2(RGPD3):​c.5054A>G​(p.Glu1685Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD3	NM_001144013.2	c.5054A>G	p.Glu1685Gly	missense_variant	Exon 21 of 23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2	c.5078A>G	p.Glu1693Gly	missense_variant	Exon 22 of 24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4	c.5054A>G	p.Glu1685Gly	missense_variant	Exon 21 of 23	1	NM_001144013.2	ENSP00000386588.4
RGPD3	ENST00000304514.11	c.5036A>G	p.Glu1679Gly	missense_variant	Exon 21 of 23	2		ENSP00000303659.8

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459688 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 726154

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5054A>G (p.E1685G) alteration is located in exon 21 (coding exon 21) of the RGPD3 gene. This alteration results from a A to G substitution at nucleotide position 5054, causing the glutamic acid (E) at amino acid position 1685 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.11	.;N
REVEL	Benign	0.12
Sift	Uncertain	0.020	.;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.99	.;D
Vest4		0.69
MutPred		0.20		.;Gain of MoRF binding (P = 0.0353);
MVP		0.29
ClinPred		0.71	D
GERP RS		0.70
Varity_R		0.067
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-107032316;