2-112388229-A-G

Variant names:

• chr2-112388229-A-G
• rs1179268976
• NM_001164463.1:c.4716T>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.4716T>C​(p.Ser1572Ser) 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: 𝑓 0.0000085 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=1.54 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.4716T>C	p.Ser1572Ser	synonymous	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>C	p.Ser1572Ser	synonymous	Exon 20 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4296T>C	p.Ser1432Ser	synonymous	Exon 19 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.2679T>C	p.Ser893Ser	synonymous	Exon 7 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes AF: 0.00000845 AC: 1 AN: 118296 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

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: 0.0000470 AC: 2 AN: 42590 AF XY: 0.0000455

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000291

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: 0.0000164 AC: 23 AN: 1403608 Hom.: 0 Cov.: 28 AF XY: 0.0000157 AC XY: 11 AN XY: 699064

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

American (AMR) AF: 0.000283 AC: 12 AN: 42404

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.000109 AC: 9 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: 0.00 AC: 0 AN: 1067646

Other (OTH) AF: 0.0000343 AC: 2 AN: 58242

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000845 AC: 1 AN: 118296 Hom.: 0 Cov.: 15 AF XY: 0.0000178 AC XY: 1 AN XY: 56058

African (AFR) AF: 0.00 AC: 0 AN: 29798

American (AMR) AF: 0.0000950 AC: 1 AN: 10528

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4284

South Asian (SAS) AF: 0.00 AC: 0 AN: 3170

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57180

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.3
DANN	Benign	0.46
PhyloP100		1.5
Mutation Taster		=99/1	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;