Variant chr3-19983742-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004162.5(RAB5A):c.567A>G(p.Pro189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,612,280 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 18 hom. )

Consequence

RAB5A
NM_004162.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

Variant links:

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]

RAB5A links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-19983742-A-G is Benign according to our data. Variant chr3-19983742-A-G is described in ClinVar as [Benign]. Clinvar id is 774418.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0066 (1005/152322) while in subpopulation AFR AF= 0.022 (915/41564). AF 95% confidence interval is 0.0208. There are 11 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1005 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RAB5A	NM_004162.5 linkuse as main transcript	c.567A>G	p.Pro189=	synonymous_variant	6/6	ENST00000273047.9
RAB5A	NM_001292048.2 linkuse as main transcript	c.525A>G	p.Pro175=	synonymous_variant	6/6
RAB5A	XM_047448648.1 linkuse as main transcript	c.306A>G	p.Pro102=	synonymous_variant	6/6
PP2D1	NR_027694.2 linkuse as main transcript	n.1385+452T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB5A	ENST00000273047.9 linkuse as main transcript	c.567A>G	p.Pro189=	synonymous_variant	6/6	1	NM_004162.5	P1	P20339-1

Frequencies

GnomAD3 genomes

AF:

0.00654

AC:

996

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00162

AC:

404

AN:

248746

Hom.:

AF XY:

0.00129

AC XY:

174

AN XY:

134544

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.000873

AC:

1274

AN:

1459958

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

570

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000814

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00660

AC:

1005

AN:

152322

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

459

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00745

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.1

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over