3-128070329-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013336.4(SEC61A1):c.*667G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,174 control chromosomes in the GnomAD database, including 3,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (3809 hom., cov: 33)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: SEC61A1 NM_013336.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC61A1	NM_013336.4	c.*667G>C		3_prime_UTR_variant	12/12	ENST00000243253.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC61A1	ENST00000243253.8	c.*667G>C		3_prime_UTR_variant	12/12	1	NM_013336.4	P4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33660 AN: 152002 Hom.: 3808 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.0556 AC: 3 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.0789 AC XY: 3 AN XY: 38

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.221 AC: 33666 AN: 152120 Hom.: 3809 Cov.: 33 AF XY: 0.222 AC XY: 16518 AN XY: 74350

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.218

Alfa AF: 0.223 Hom.: 489

Bravo AF: 0.211

Asia WGS AF: 0.179 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.44
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1042907; hg19: chr3-127789172;