3-128065275-T-C

Variant names:

• chr3-128065275-T-C
• rs13070488
• NM_013336.4:c.777+238T>C

Variant summary

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

The NM_013336.4(SEC61A1):​c.777+238T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 615,992 control chromosomes in the GnomAD database, including 17,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4130 hom., cov: 33)
  • Exomes 𝑓: 0.23 (13296 hom.)
• Consequence: SEC61A1 NM_013336.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.100
• Publications: 5 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=-0.93).
• BP6: Variant 3-128065275-T-C is Benign according to our data. Variant chr3-128065275-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 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.777+238T>C		intron	N/A	NP_037468.1	B3KNF6
	SEC61A1	NM_001400328.1		c.795+238T>C		intron	N/A	NP_001387257.1	B4DR61
	SEC61A1	NM_001400329.1		c.618+238T>C		intron	N/A	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.777+238T>C		intron	N/A	ENSP00000243253.3	P61619-1
	SEC61A1	ENST00000483956.2	TSL:1	n.*173+19T>C		intron	N/A	ENSP00000514247.1	A0A8V8TNG8
	SEC61A1	ENST00000937479.1		c.777+238T>C		intron	N/A	ENSP00000607538.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35160 AN: 152108 Hom.: 4130 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.232 AC: 107396 AN: 463764 Hom.: 13296 Cov.: 4 AF XY: 0.234 AC XY: 57190 AN XY: 244776

African (AFR) AF: 0.243 AC: 3145 AN: 12960

American (AMR) AF: 0.151 AC: 3101 AN: 20580

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 3978 AN: 14304

East Asian (EAS) AF: 0.0730 AC: 2287 AN: 31328

South Asian (SAS) AF: 0.264 AC: 12617 AN: 47764

European-Finnish (FIN) AF: 0.270 AC: 8241 AN: 30550

Middle Eastern (MID) AF: 0.259 AC: 942 AN: 3636

European-Non Finnish (NFE) AF: 0.242 AC: 66704 AN: 275860

Other (OTH) AF: 0.238 AC: 6381 AN: 26782

GnomAD4 genome AF: 0.231 AC: 35164 AN: 152228 Hom.: 4130 Cov.: 33 AF XY: 0.231 AC XY: 17224 AN XY: 74444

African (AFR) AF: 0.232 AC: 9644 AN: 41520

American (AMR) AF: 0.171 AC: 2612 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 928 AN: 3468

East Asian (EAS) AF: 0.0842 AC: 437 AN: 5190

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4830

European-Finnish (FIN) AF: 0.261 AC: 2773 AN: 10606

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

European-Non Finnish (NFE) AF: 0.244 AC: 16568 AN: 67996

Other (OTH) AF: 0.227 AC: 481 AN: 2116

Alfa AF: 0.238 Hom.: 2819

Bravo AF: 0.222

Asia WGS AF: 0.183 AC: 640 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		0.10
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)		0.010		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: rs13070488; hg19: chr3-127784118; COSMIC: COSV107291412; COSMIC: COSV107291412;