rs1168709911

Variant names:

• chr2-86974217-C-G
• rs1168709911
• NM_001382344.1:c.1418C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-86974217-C-G
• chr2-86974217-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001382344.1(RGPD1):​c.1418C>G​(p.Thr473Arg) variant causes a missense change. In-silico tool predicts 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. T473I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41746807).

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.1418C>G	p.Thr473Arg	missense	Exon 10 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.1418C>G	p.Thr473Arg	missense	Exon 10 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.1394C>G	p.Thr465Arg	missense	Exon 10 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.1418C>G	p.Thr473Arg	missense	Exon 10 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.1418C>G	p.Thr473Arg	missense	Exon 10 of 23	ENSP00000381253.3	F8VYC4

Frequencies

GnomAD3 genomes AF: 0.0000163 AC: 2 AN: 122664 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000645

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000505 AC: 70 AN: 1385320 Hom.: 0 Cov.: 25 AF XY: 0.0000551 AC XY: 38 AN XY: 689848

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000324 AC: 1 AN: 30832

American (AMR) AF: 0.00 AC: 0 AN: 43092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25200

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.00 AC: 0 AN: 84256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3930

European-Non Finnish (NFE) AF: 0.0000630 AC: 66 AN: 1047928

Other (OTH) AF: 0.0000520 AC: 3 AN: 57714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000163 AC: 2 AN: 122664 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 58940

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000645 AC: 2 AN: 31000

American (AMR) AF: 0.00 AC: 0 AN: 12392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3000

East Asian (EAS) AF: 0.00 AC: 0 AN: 4474

South Asian (SAS) AF: 0.00 AC: 0 AN: 3686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57938

Other (OTH) AF: 0.00 AC: 0 AN: 1552

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.081	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.74
MutPred		0.22		Gain of solvent accessibility (P = 0.026)
MVP		0.25
ClinPred		0.96	D
GERP RS		2.3
Varity_R		0.50
gMVP		0.13
Mutation Taster		=99/1	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: rs1168709911; hg19: chr2-87201340;