2-112388408-C-T

Variant names:

• chr2-112388408-C-T
• rs780242612
• NM_001164463.1:c.4537G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164463.1(RGPD8):​c.4537G>A​(p.Ala1513Thr) 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: 𝑓 0.000096 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000070 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03417945).

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.4537G>A	p.Ala1513Thr	missense	Exon 20 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.4537G>A	p.Ala1513Thr	missense	Exon 20 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4117G>A	p.Ala1373Thr	missense	Exon 19 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.2500G>A	p.Ala834Thr	missense	Exon 7 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes AF: 0.0000962 AC: 12 AN: 124752 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000290 AC: 6 AN: 206586 AF XY: 0.00

Gnomad AFR exome AF: 0.000380

Gnomad AMR exome AF: 0.0000332

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000699 AC: 10 AN: 1431458 Hom.: 0 Cov.: 33 AF XY: 0.00000842 AC XY: 6 AN XY: 712360

African (AFR) AF: 0.000242 AC: 8 AN: 33114

American (AMR) AF: 0.0000225 AC: 1 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25524

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 84656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088364

Other (OTH) AF: 0.0000169 AC: 1 AN: 59246

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000962 AC: 12 AN: 124752 Hom.: 0 Cov.: 16 AF XY: 0.0000668 AC XY: 4 AN XY: 59874

African (AFR) AF: 0.000237 AC: 8 AN: 33824

American (AMR) AF: 0.000335 AC: 4 AN: 11940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2952

East Asian (EAS) AF: 0.00 AC: 0 AN: 4632

South Asian (SAS) AF: 0.00 AC: 0 AN: 3360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57800

Other (OTH) AF: 0.00 AC: 0 AN: 1616

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000350 AC: 4

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	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.37
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.032
Sift	Benign	0.39	T
Sift4G	Benign	0.31	T
Polyphen		0.0070	B
Vest4		0.035
MVP		0.014
ClinPred		0.0074	T
GERP RS		0.23
Varity_R		0.030
gMVP		0.013
Mutation Taster		=83/17	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: rs780242612; hg19: chr2-113145985;