rs1441673774

Variant names:

• chr2-86986771-C-T
• rs1441673774
• NM_001382344.1:c.3872C>T

Variant summary

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

The NM_001382344.1(RGPD1):​c.3872C>T​(p.Ala1291Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 8)
  • Exomes 𝑓: 0.00023 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• 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=0.08546522).

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.3872C>T	p.Ala1291Val	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.3872C>T	p.Ala1291Val	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.3848C>T	p.Ala1283Val	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.3872C>T	p.Ala1291Val	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.3872C>T	p.Ala1291Val	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
	RGPD1	ENST00000428128.1	TSL:1	n.*1791C>T		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes AF: 0.000324 AC: 18 AN: 55486 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00435

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000296

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000233 AC: 312 AN: 1338112 Hom.: 2 Cov.: 21 AF XY: 0.000243 AC XY: 163 AN XY: 670440

African (AFR) AF: 0.0000908 AC: 2 AN: 22016

American (AMR) AF: 0.0000687 AC: 3 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.00491 AC: 124 AN: 25276

East Asian (EAS) AF: 0.00 AC: 0 AN: 38726

South Asian (SAS) AF: 0.00 AC: 0 AN: 83512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52520

Middle Eastern (MID) AF: 0.000257 AC: 1 AN: 3894

European-Non Finnish (NFE) AF: 0.000152 AC: 154 AN: 1012800

Other (OTH) AF: 0.000503 AC: 28 AN: 55694

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000324 AC: 18 AN: 55486 Hom.: 0 Cov.: 8 AF XY: 0.000193 AC XY: 5 AN XY: 25926

African (AFR) AF: 0.00 AC: 0 AN: 7482

American (AMR) AF: 0.00 AC: 0 AN: 4692

Ashkenazi Jewish (ASJ) AF: 0.00435 AC: 8 AN: 1838

East Asian (EAS) AF: 0.00 AC: 0 AN: 1982

South Asian (SAS) AF: 0.00 AC: 0 AN: 1124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 136

European-Non Finnish (NFE) AF: 0.000296 AC: 10 AN: 33742

Other (OTH) AF: 0.00 AC: 0 AN: 530

Alfa AF: 0.000337 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.0011
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.081
Sift	Benign	0.082	T
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.16
MVP		0.16
ClinPred		0.84	D
GERP RS		2.4
Varity_R		0.11
gMVP		0.021
Mutation Taster		=94/6	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: rs1441673774; hg19: chr2-87213894;