NM_001144013.2:c.5039A>T

Variant names:

• chr2-106415875-T-A
• rs199544143
• NM_001144013.2:c.5039A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001144013.2(RGPD3):​c.5039A>T​(p.Asn1680Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. N1680S) 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 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.5039A>T	p.Asn1680Ile	missense_variant	Exon 21 of 23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2	c.5063A>T	p.Asn1688Ile	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.5039A>T	p.Asn1680Ile	missense_variant	Exon 21 of 23	1	NM_001144013.2	ENSP00000386588.4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0075	.;T
Eigen	Benign	0.080
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	.;L
PhyloP100		5.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.99	.;N
REVEL	Benign	0.18
Sift	Uncertain	0.010	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.99	.;D
Vest4		0.81
MutPred		0.37		.;Loss of loop (P = 0.0288);
MVP		0.24
ClinPred		0.62	D
GERP RS		0.70
Varity_R		0.16
gMVP		0.086
Mutation Taster		=100/0	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: rs199544143; hg19: chr2-107032331;