chr3-128064855-A-T

Variant names:

• chr3-128064855-A-T
• rs1044843
• NM_013336.4:c.617-22A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.37
• Publications: 12 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319086.1. 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
	SEC61A1	NM_013336.4	MANE Select	c.617-22A>T		intron	N/A	NP_037468.1	B3KNF6
	RUVBL1	NM_001319086.1		c.*357T>A		3_prime_UTR	Exon 10 of 10	NP_001306015.1	E7ETR0
	SEC61A1	NM_001400328.1		c.635-22A>T		intron	N/A	NP_001387257.1	B4DR61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61A1	ENST00000243253.8	TSL:1 MANE Select	c.617-22A>T		intron	N/A	ENSP00000243253.3	P61619-1
	SEC61A1	ENST00000483956.2	TSL:1	n.617-22A>T		intron	N/A	ENSP00000514247.1	A0A8V8TNG8
	RUVBL1	ENST00000881248.1		c.*402T>A		3_prime_UTR	Exon 12 of 12	ENSP00000551307.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35150 AN: 152010 Hom.: 4128 Cov.: 33

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

GnomAD2 exomes AF: 0.220 AC: 47312 AN: 215110 AF XY: 0.225

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 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.: 31 AF XY: 0.236 AC XY: 164137 AN XY: 696748

African (AFR) AF: 0.241 AC: 7694 AN: 31876

American (AMR) AF: 0.136 AC: 5184 AN: 38110

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 6218 AN: 22788

East Asian (EAS) AF: 0.0742 AC: 2919 AN: 39328

South Asian (SAS) AF: 0.264 AC: 20418 AN: 77362

European-Finnish (FIN) AF: 0.272 AC: 14041 AN: 51630

Middle Eastern (MID) AF: 0.249 AC: 1360 AN: 5454

European-Non Finnish (NFE) AF: 0.239 AC: 259483 AN: 1086496

Other (OTH) AF: 0.237 AC: 13839 AN: 58280

GnomAD4 genome AF: 0.231 AC: 35154 AN: 152128 Hom.: 4128 Cov.: 33 AF XY: 0.232 AC XY: 17220 AN XY: 74364

African (AFR) AF: 0.232 AC: 9638 AN: 41484

American (AMR) AF: 0.171 AC: 2614 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3470

East Asian (EAS) AF: 0.0844 AC: 437 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2773 AN: 10582

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16563 AN: 67980

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.236 Hom.: 834

Bravo AF: 0.222

Asia WGS AF: 0.183 AC: 641 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.74
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs1044843; hg19: chr3-127783698; COSMIC: COSV54576807; COSMIC: COSV54576807;