2-106415860-T-G

Variant names:

• chr2-106415860-T-G
• rs772474940
• NM_001144013.2:c.5054A>C

Variant summary

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

The NM_001144013.2(RGPD3):​c.5054A>C​(p.Glu1685Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1685G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 27)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• 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=0.39581043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD3	NM_001144013.2	c.5054A>C	p.Glu1685Ala	missense_variant	Exon 21 of 23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2	c.5078A>C	p.Glu1693Ala	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>C	p.Glu1685Ala	missense_variant	Exon 21 of 23	1	NM_001144013.2	ENSP00000386588.4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244600 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0056	.;T
Eigen	Benign	0.086
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	.;M
PhyloP100		5.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.13	.;N
REVEL	Benign	0.12
Sift	Benign	0.045	.;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.98	.;D
Vest4		0.70
MutPred		0.19		.;Gain of MoRF binding (P = 0.033);
MVP		0.25
ClinPred		0.56	D
GERP RS		0.70
Varity_R		0.051
gMVP		0.10
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs772474940; hg19: chr2-107032316;