NM_001164463.1:c.5058T>C

Variant names:

• chr2-112380827-A-G
• rs1398138299
• NM_001164463.1:c.5058T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001164463.1(RGPD8):​c.5058T>C​(p.Ile1686Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.299 with no splicing effect.

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.5058T>C	p.Ile1686Ile	synonymous	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.5058T>C	p.Ile1686Ile	synonymous	Exon 21 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4638T>C	p.Ile1546Ile	synonymous	Exon 20 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.3021T>C	p.Ile1007Ile	synonymous	Exon 8 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000156 AC: 2 AN: 1282656 Hom.: 0 Cov.: 30 AF XY: 0.00000313 AC XY: 2 AN XY: 639520

African (AFR) AF: 0.00 AC: 0 AN: 31058

American (AMR) AF: 0.00 AC: 0 AN: 37224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23416

East Asian (EAS) AF: 0.0000530 AC: 2 AN: 37770

South Asian (SAS) AF: 0.00 AC: 0 AN: 73312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 973500

Other (OTH) AF: 0.00 AC: 0 AN: 53852

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.9
DANN	Benign	0.64
PhyloP100		0.30
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: rs1398138299; hg19: chr2-113138404;