3-19984917-C-G

Position:

• chr3-19984917-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000273047.9(RAB5A):​c.*1094C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 154,100 control chromosomes in the GnomAD database, including 3,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3905 hom., cov: 32)
  • Exomes 𝑓: 0.13 (17 hom.)
• Consequence: RAB5A ENST00000273047.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.822

Genes affected

RAB5A (HGNC:9783): (RAB5A, member RAS oncogene family) Enables GDP binding activity; GTP binding activity; and GTPase activity. Involved in several processes, including amyloid-beta clearance by transcytosis; early endosome to late endosome transport; and regulation of exocytosis. Located in several cellular components, including cytoplasmic side of early endosome membrane; nucleoplasm; and terminal bouton. [provided by Alliance of Genome Resources, Apr 2022]

PP2D1 (HGNC:28406): (protein phosphatase 2C like domain containing 1) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

PP2D1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-19984917-C-G is Benign according to our data. Variant chr3-19984917-C-G is described in ClinVar as [Benign]. Clinvar id is 1178729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5A	NM_004162.5	c.*1094C>G		3_prime_UTR_variant	6/6	ENST00000273047.9	NP_004153.2
RAB5A	NM_001292048.2	c.*1094C>G		3_prime_UTR_variant	6/6		NP_001278977.1
RAB5A	XM_047448648.1	c.*1094C>G		3_prime_UTR_variant	6/6		XP_047304604.1
PP2D1	NR_027694.2	n.1283-621G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB5A	ENST00000273047.9	c.*1094C>G		3_prime_UTR_variant	6/6	1	NM_004162.5	ENSP00000273047.4
PP2D1	ENST00000333083.11	n.1091-621G>C		intron_variant		1		ENSP00000331295.7

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31361 AN: 151906 Hom.: 3901 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.134 AC: 278 AN: 2078 Hom.: 17 Cov.: 0 AF XY: 0.126 AC XY: 151 AN XY: 1198

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.206 AC: 31376 AN: 152022 Hom.: 3905 Cov.: 32 AF XY: 0.205 AC XY: 15197 AN XY: 74306

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.186

Alfa AF: 0.175 Hom.: 369

Bravo AF: 0.210

Asia WGS AF: 0.185 AC: 644 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2021	This variant is associated with the following publications: (PMID: 28171541) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.6
DANN	Benign	0.85

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: rs8682; hg19: chr3-20026409;