2-106415878-G-C

Variant names:

• chr2-106415878-G-C
• NM_001144013.2:c.5036C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144013.2(RGPD3):​c.5036C>G​(p.Thr1679Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.35

Genes affected

RGPD3 (HGNC:32416): (RANBP2 like and GRIP domain containing 3) This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26208073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD3	NM_001144013.2	c.5036C>G	p.Thr1679Ser	missense_variant	Exon 21 of 23	ENST00000409886.4	NP_001137485.1
RGPD3	XM_017004738.2	c.5060C>G	p.Thr1687Ser	missense_variant	Exon 22 of 24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4	c.5036C>G	p.Thr1679Ser	missense_variant	Exon 21 of 23	1	NM_001144013.2	ENSP00000386588.4
RGPD3	ENST00000304514.11	c.5018C>G	p.Thr1673Ser	missense_variant	Exon 21 of 23	2		ENSP00000303659.8

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459694 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 726156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.0028	.;T
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.37	.;N
REVEL	Benign	0.15
Sift	Uncertain	0.029	.;D
Sift4G	Benign	0.16	T;T
Polyphen		0.98	.;D
Vest4		0.50
MutPred		0.21		.;Loss of catalytic residue at T1679 (P = 0.033);
MVP		0.076
ClinPred		0.56	D
GERP RS		0.70
Varity_R		0.058
gMVP		0.041

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-107032334;