2-86986735-A-C

Position:

• chr2-86986735-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382344.1(RGPD1):​c.3836A>C​(p.Glu1279Ala) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.12

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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]

RGPD1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2472929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1	c.3836A>C	p.Glu1279Ala	missense_variant	20/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD1	ENST00000641458.2	c.3836A>C	p.Glu1279Ala	missense_variant	20/23		NM_001382344.1	ENSP00000492954.1
RGPD1	ENST00000398193.8	c.3836A>C	p.Glu1279Ala	missense_variant	20/23	1		ENSP00000381253.3
RGPD1	ENST00000428128.1	n.*1755A>C		non_coding_transcript_exon_variant	7/10	1		ENSP00000402729.1
RGPD1	ENST00000428128.1	n.*1755A>C		3_prime_UTR_variant	7/10	1		ENSP00000402729.1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.80e-7 AC: 1 AN: 1136200 Hom.: 0 Cov.: 15 AF XY: 0.00000174 AC XY: 1 AN XY: 574428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.3812A>C (p.E1271A) alteration is located in exon 20 (coding exon 20) of the RGPD1 gene. This alteration results from a A to C substitution at nucleotide position 3812, causing the glutamic acid (E) at amino acid position 1271 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T;.;T;.
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.093
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D;D;D;.
REVEL	Benign	0.26
Sift	Benign	0.076	T;T;T;.
Sift4G	Uncertain	0.033	D;D;D;.
Polyphen		0.87	.;P;.;.
Vest4		0.28
MutPred		0.18		.;Gain of catalytic residue at E1279 (P = 0.0258);.;Gain of catalytic residue at E1279 (P = 0.0258);
MVP		0.15
ClinPred		0.67	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.044

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

Publications

LitVar

Other links and lift over

dbSNP: rs1681474589; hg19: chr2-87213858;