rs1370191714

Variant names:

• chr2-112388152-G-A
• NM_001164463.1:c.4793C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-112388152-G-A
• chr2-112388152-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164463.1(RGPD8):​c.4793C>T​(p.Pro1598Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1598R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.113339245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD8	NM_001164463.1	c.4793C>T	p.Pro1598Leu	missense_variant	Exon 20 of 23	ENST00000302558.8	NP_001157935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8	c.4793C>T	p.Pro1598Leu	missense_variant	Exon 20 of 23	1	NM_001164463.1	ENSP00000306637.3
RGPD8	ENST00000409750.5	c.4373C>T	p.Pro1458Leu	missense_variant	Exon 19 of 22	1		ENSP00000386511.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome AF: 8.80e-7 AC: 1 AN: 1136288 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 569726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000348

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.013	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.037
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.52	T;T
Polyphen		0.98	D;.
Vest4		0.098
MutPred		0.27		Gain of sheet (P = 0.0266);.;
MVP		0.16
ClinPred		0.52	D
GERP RS		1.3
Varity_R		0.16
gMVP		0.017

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113145729;