chr2-107827066-C-A

Variant names:

• chr2-107827066-C-A
• rs767496590
• NM_182588.3:c.53C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182588.3(RGPD4):​c.53C>A​(p.Ser18Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,440,716 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. 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. S18F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RGPD4 NM_182588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) 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]

RGPD4-AS1 (HGNC:49273): (RGPD4 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22529918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182588.3. 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
	RGPD4	NM_182588.3	MANE Select	c.53C>A	p.Ser18Tyr	missense	Exon 1 of 23	NP_872394.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD4	ENST00000408999.4	TSL:1 MANE Select	c.53C>A	p.Ser18Tyr	missense	Exon 1 of 23	ENSP00000386810.4	Q7Z3J3-1
	RGPD4-AS1	ENST00000457647.2	TSL:1	n.-175G>T		upstream_gene	N/A
	RGPD4-AS1	ENST00000417284.3	TSL:2	n.-237G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1440716 Hom.: 0 Cov.: 59 AF XY: 0.00000140 AC XY: 1 AN XY: 714614

African (AFR) AF: 0.00 AC: 0 AN: 32990

American (AMR) AF: 0.00 AC: 0 AN: 42220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 38936

South Asian (SAS) AF: 0.00 AC: 0 AN: 82738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1103026

Other (OTH) AF: 0.00 AC: 0 AN: 59584

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.056
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.84	P
Vest4		0.43
MutPred		0.27		Loss of glycosylation at S18 (P = 0.0122)
MVP		0.061
ClinPred		0.32	T
GERP RS		1.4
PromoterAI		-0.052	Neutral
Varity_R		0.088
gMVP		0.012
Mutation Taster		=99/1	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: rs767496590; hg19: chr2-108443522; COSMIC: COSV61747777; COSMIC: COSV61747777;