NM_001164463.1:c.4716T>G

Variant names:

• chr2-112388229-A-C
• rs1179268976
• NM_001164463.1:c.4716T>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.4716T>G​(p.Ser1572Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.121480465).

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.4716T>G	p.Ser1572Arg	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.4716T>G	p.Ser1572Arg	missense	Exon 20 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4296T>G	p.Ser1432Arg	missense	Exon 19 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.2679T>G	p.Ser893Arg	missense	Exon 7 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes AF: 0.0000338 AC: 4 AN: 118296 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000467

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000175

Gnomad OTH AF: 0.000663

GnomAD2 exomes AF: 0.0000704 AC: 3 AN: 42590 AF XY: 0.000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000323

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000629

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000271 AC: 38 AN: 1403602 Hom.: 0 Cov.: 28 AF XY: 0.0000386 AC XY: 27 AN XY: 699064

African (AFR) AF: 0.00 AC: 0 AN: 31904

American (AMR) AF: 0.00 AC: 0 AN: 42406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39336

South Asian (SAS) AF: 0.000230 AC: 19 AN: 82646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52212

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

European-Non Finnish (NFE) AF: 0.0000140 AC: 15 AN: 1067644

Other (OTH) AF: 0.0000172 AC: 1 AN: 58238

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000338 AC: 4 AN: 118370 Hom.: 0 Cov.: 15 AF XY: 0.0000534 AC XY: 3 AN XY: 56154

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

African (AFR) AF: 0.00 AC: 0 AN: 29894

American (AMR) AF: 0.00 AC: 0 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2878

East Asian (EAS) AF: 0.000468 AC: 2 AN: 4272

South Asian (SAS) AF: 0.00 AC: 0 AN: 3154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000175 AC: 1 AN: 57172

Other (OTH) AF: 0.000654 AC: 1 AN: 1530

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000388202), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.91	P
Vest4		0.22
MutPred		0.32		Gain of methylation at S1572 (P = 0.014)
MVP		0.12
ClinPred		0.20	T
GERP RS		1.1
Varity_R		0.24
gMVP		0.045
Mutation Taster		=96/4	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: rs1179268976; hg19: chr2-113145806;