chr2-106423139-T-C

Variant names:

• chr2-106423139-T-C
• rs202089546
• NM_001144013.2:c.4828A>G

Variant summary

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

The NM_001144013.2(RGPD3):​c.4828A>G​(p.Ile1610Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD3 NM_001144013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15
• Publications: 0 publications found

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]

ENSG00000291125 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029238522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144013.2. 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
	RGPD3	NM_001144013.2	MANE Select	c.4828A>G	p.Ile1610Val	missense	Exon 20 of 23	NP_001137485.1	A6NKT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD3	ENST00000409886.4	TSL:1 MANE Select	c.4828A>G	p.Ile1610Val	missense	Exon 20 of 23	ENSP00000386588.4	A6NKT7
	RGPD3	ENST00000304514.11	TSL:2	c.4810A>G	p.Ile1604Val	missense	Exon 20 of 23	ENSP00000303659.8	J3KNE0
	ENSG00000291125	ENST00000779577.1		n.469-24182T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152118 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000855 AC: 13 AN: 152030 AF XY: 0.0000969

Gnomad AFR exome AF: 0.0000880

Gnomad AMR exome AF: 0.0000457

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000101 AC: 144 AN: 1419646 Hom.: 0 Cov.: 28 AF XY: 0.0000977 AC XY: 69 AN XY: 706280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000313 AC: 1 AN: 31996

American (AMR) AF: 0.0000717 AC: 3 AN: 41822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25244

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.00 AC: 0 AN: 82886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.000127 AC: 138 AN: 1083410

Other (OTH) AF: 0.0000342 AC: 2 AN: 58546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000855 AC: 13 AN: 152118 Hom.: 0 Cov.: 28 AF XY: 0.0000538 AC XY: 4 AN XY: 74302

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000505218), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000159 Hom.: 0

ExAC AF: 0.0000720 AC: 8

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	0.065
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.071
DANN	Benign	0.50
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		-1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.017
Sift	Benign	0.27	T
Sift4G	Benign	0.92	T
Polyphen		0.0010	B
Vest4		0.081
MutPred		0.15		Loss of methylation at K1606 (P = 0.1216)
MVP		0.014
ClinPred		0.014	T
GERP RS		-4.2
Varity_R		0.030
gMVP		0.0089
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: rs202089546; hg19: chr2-107039595;