2-112380948-T-C

Variant names:

• chr2-112380948-T-C
• rs1490160676
• NM_001164463.1:c.4937A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164463.1(RGPD8):​c.4937A>G​(p.His1646Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07189283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164463.1. 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
	RGPD8	NM_001164463.1	MANE Select	c.4937A>G	p.His1646Arg	missense	Exon 21 of 23	NP_001157935.1	O14715

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD8	ENST00000302558.8	TSL:1 MANE Select	c.4937A>G	p.His1646Arg	missense	Exon 21 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4517A>G	p.His1506Arg	missense	Exon 20 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.2900A>G	p.His967Arg	missense	Exon 8 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD2 exomes AF: 0.00000637 AC: 1 AN: 157096 AF XY: 0.0000119

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: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000840 AC: 8 AN: 952036 Hom.: 0 Cov.: 14 AF XY: 0.00000619 AC XY: 3 AN XY: 484824

African (AFR) AF: 0.00 AC: 0 AN: 25712

American (AMR) AF: 0.00 AC: 0 AN: 35218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21064

East Asian (EAS) AF: 0.00 AC: 0 AN: 36052

South Asian (SAS) AF: 0.00 AC: 0 AN: 64382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3130

European-Non Finnish (NFE) AF: 0.0000118 AC: 8 AN: 677464

Other (OTH) AF: 0.00 AC: 0 AN: 43202

GnomAD4 genome Cov.: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.031
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.023	D
Polyphen		0.063	B
Vest4		0.15
MutPred		0.28		Loss of helix (P = 0.0093)
MVP		0.014
ClinPred		0.10	T
GERP RS		0.72
Varity_R		0.11
gMVP		0.012
Mutation Taster		=97/3	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: rs1490160676; hg19: chr2-113138525;