3-128070329-G-C

Variant names:

• chr3-128070329-G-C
• rs1042907
• NM_013336.4:c.*667G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013336.4. 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.*667G>C		3_prime_UTR	Exon 12 of 12	NP_037468.1	B3KNF6
	SEC61A1	NM_001400328.1		c.*667G>C		3_prime_UTR	Exon 12 of 12	NP_001387257.1	B4DR61
	SEC61A1	NM_001400329.1		c.*667G>C		3_prime_UTR	Exon 11 of 11	NP_001387258.1	C9JXC6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61A1	ENST00000243253.8	TSL:1 MANE Select	c.*667G>C		3_prime_UTR	Exon 12 of 12	ENSP00000243253.3	P61619-1
	SEC61A1	ENST00000483956.2	TSL:1	n.*1589G>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000514247.1	A0A8V8TNG8
	SEC61A1	ENST00000483956.2	TSL:1	n.*1589G>C		3_prime_UTR	Exon 14 of 14	ENSP00000514247.1	A0A8V8TNG8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0476 AC: 2 AN: 42

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.200 AC: 8310 AN: 41502

American (AMR) AF: 0.164 AC: 2501 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 932 AN: 3472

East Asian (EAS) AF: 0.0832 AC: 431 AN: 5182

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2761 AN: 10560

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16553 AN: 67986

Other (OTH) AF: 0.218 AC: 461 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.73
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1042907; hg19: chr3-127789172;