NM_182588.3:c.40T>G

Variant names:

• chr2-107827053-T-G
• rs777148860
• NM_182588.3:c.40T>G

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.40T>G​(p.Ser14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S14C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: RGPD4 NM_182588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• 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=0.13805804).

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.40T>G	p.Ser14Ala	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.40T>G	p.Ser14Ala	missense	Exon 1 of 23	ENSP00000386810.4	Q7Z3J3-1
	RGPD4-AS1	ENST00000457647.2	TSL:1	n.-162A>C		upstream_gene	N/A
	RGPD4-AS1	ENST00000417284.3	TSL:2	n.-224A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000139 AC: 3 AN: 216256 AF XY: 0.00000859

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1445294 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 717294

African (AFR) AF: 0.00 AC: 0 AN: 33094

American (AMR) AF: 0.00 AC: 0 AN: 42936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39172

South Asian (SAS) AF: 0.0000601 AC: 5 AN: 83194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105462

Other (OTH) AF: 0.00 AC: 0 AN: 59754

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000833 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.14	T
Sift4G	Uncertain	0.013	D
Polyphen		0.34	B
Vest4		0.43
MutPred		0.23		Loss of phosphorylation at S14 (P = 0.0457)
MVP		0.055
ClinPred		0.060	T
GERP RS		1.1
PromoterAI		0.041	Neutral
Varity_R		0.12
gMVP		0.0090
Mutation Taster		=98/2	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: rs777148860; hg19: chr2-108443509;