rs199544143

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-106415875-T-C
• chr2-106415875-T-A

Variant summary

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

The NM_001144013.2(RGPD3):​c.5039A>G​(p.Asn1680Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,611,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.34196627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144013.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD3	NM_001144013.2	MANE Select	c.5039A>G	p.Asn1680Ser	missense	Exon 21 of 23	NP_001137485.1	A6NKT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD3	ENST00000409886.4	TSL:1 MANE Select	c.5039A>G	p.Asn1680Ser	missense	Exon 21 of 23	ENSP00000386588.4	A6NKT7
	RGPD3	ENST00000304514.11	TSL:2	c.5021A>G	p.Asn1674Ser	missense	Exon 21 of 23	ENSP00000303659.8	J3KNE0
	ENSG00000291125	ENST00000779577.1		n.468+24855T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152112 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249308 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1459694 Hom.: 0 Cov.: 40 AF XY: 0.00000689 AC XY: 5 AN XY: 726156

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111822

Other (OTH) AF: 0.0000166 AC: 1 AN: 60204

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 27 AF XY: 0.0000134 AC XY: 1 AN XY: 74410

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000315 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.15
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.15
Sift	Benign	0.95	T
Sift4G	Benign	0.62	T
Polyphen		0.98	D
Vest4		0.68
MVP		0.067
ClinPred		0.22	T
GERP RS		0.70
Varity_R		0.033
gMVP		0.046
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;