3-128064855-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001319086.1(RUVBL1):c.*357T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,563,452 control chromosomes in the GnomAD database, including 44,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4128 hom., cov: 33)

Exomes 𝑓: 0.23 ( 40236 hom. )

Consequence

RUVBL1
NM_001319086.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.37

Variant links:

Genes affected

SEC61A1 (HGNC:18276): (SEC61 translocon subunit alpha 1) The protein encoded by this gene belongs to the SECY/SEC61- alpha family. It appears to play a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. This protein found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins. This gene encodes an alpha subunit of the heteromeric SEC61 complex, which also contains beta and gamma subunits. [provided by RefSeq, Jul 2008]

SEC61A1 links:

RUVBL1 (HGNC:10474): (RuvB like AAA ATPase 1) This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RUVBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-128064855-A-T is Benign according to our data. Variant chr3-128064855-A-T is described in ClinVar as [Benign]. Clinvar id is 1183327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61A1	NM_013336.4 link	c.617-22A>T		intron_variant	Intron 7 of 11	ENST00000243253.8	NP_037468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61A1	ENST00000243253.8 link	c.617-22A>T		intron_variant	Intron 7 of 11	1	NM_013336.4	ENSP00000243253.3		P61619-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35150

AN:

152010

Hom.:

4128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.0842

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.220

AC:

47312

AN:

215110

Hom.:

5546

AF XY:

0.225

AC XY:

25791

AN XY:

114728

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.0833

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.235

AC:

331156

AN:

1411324

Hom.:

40236

Cov.:

AF XY:

0.236

AC XY:

164137

AN XY:

696748

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.0742

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.231

AC:

35154

AN:

152128

Hom.:

4128

Cov.:

AF XY:

0.232

AC XY:

17220

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.0844

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.236

Hom.:

834

Bravo

AF:

0.222

Asia WGS

AF:

0.183

AC:

641

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

DANN

Benign

0.74

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