NM_001144013.2:c.5108A>C

Variant names:

• chr2-106413242-T-G
• rs566226760
• NM_001144013.2:c.5108A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001144013.2(RGPD3):​c.5108A>C​(p.Gln1703Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000454 in 1,611,996 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. Q1703R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00047 (4 hom.)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005361259).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.5108A>C	p.Gln1703Pro	missense	Exon 22 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.5108A>C	p.Gln1703Pro	missense	Exon 22 of 23	ENSP00000386588.4	A6NKT7
	RGPD3	ENST00000304514.11	TSL:2	c.5090A>C	p.Gln1697Pro	missense	Exon 22 of 23	ENSP00000303659.8	J3KNE0
	ENSG00000291125	ENST00000779577.1		n.468+22222T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152184 Hom.: 1 Cov.: 29

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: 0.00955

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000988 AC: 248 AN: 251086 AF XY: 0.00132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000469 AC: 684 AN: 1459696 Hom.: 4 Cov.: 31 AF XY: 0.000662 AC XY: 481 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: 0.00713 AC: 614 AN: 86160

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111824

Other (OTH) AF: 0.000598 AC: 36 AN: 60206

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152300 Hom.: 1 Cov.: 29 AF XY: 0.000551 AC XY: 41 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00956 AC: 46 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.00119 AC: 144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Benign	0.60
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.15
Sift	Benign	0.053	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.0010	B
Vest4		0.45
MutPred		0.14		Loss of helix (P = 0.0104)
MVP		0.030
ClinPred		0.028	T
GERP RS		-0.035
Varity_R		0.12
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs566226760; hg19: chr2-107029698;