rs1681474589

Variant names:

• chr2-86986735-A-C
• rs1681474589
• NM_001382344.1:c.3836A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382344.1(RGPD1):​c.3836A>C​(p.Glu1279Ala) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.12
• Publications: 0 publications found

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2472929).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382344.1. 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
	RGPD1	NM_001382344.1	MANE Select	c.3836A>C	p.Glu1279Ala	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.3836A>C	p.Glu1279Ala	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.3812A>C	p.Glu1271Ala	missense	Exon 20 of 23	NP_001019628.3	P0DJD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD1	ENST00000641458.2	MANE Select	c.3836A>C	p.Glu1279Ala	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.3836A>C	p.Glu1279Ala	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
	RGPD1	ENST00000428128.1	TSL:1	n.*1755A>C		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.80e-7 AC: 1 AN: 1136200 Hom.: 0 Cov.: 15 AF XY: 0.00000174 AC XY: 1 AN XY: 574428

African (AFR) AF: 0.00 AC: 0 AN: 18674

American (AMR) AF: 0.00 AC: 0 AN: 39704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23362

East Asian (EAS) AF: 0.00 AC: 0 AN: 37332

South Asian (SAS) AF: 0.00 AC: 0 AN: 77274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3456

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 836316

Other (OTH) AF: 0.00 AC: 0 AN: 49006

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

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	0.20
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.093
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.1
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.26
Sift	Benign	0.076	T
Sift4G	Uncertain	0.033	D
Polyphen		0.87	P
Vest4		0.28
MutPred		0.18		Gain of catalytic residue at E1279 (P = 0.0258)
MVP		0.15
ClinPred		0.67	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.044
Mutation Taster		=97/3	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: rs1681474589; hg19: chr2-87213858;