3-128066758-C-T

Variant names:

• chr3-128066758-C-T
• rs11714729
• NM_013336.4:c.778-196C>T

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.778-196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 589,888 control chromosomes in the GnomAD database, including 2,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (582 hom., cov: 32)
  • Exomes 𝑓: 0.097 (2290 hom.)
• Consequence: SEC61A1 NM_013336.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.563
• Publications: 2 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=-0.88).
• BP6: Variant 3-128066758-C-T is Benign according to our data. Variant chr3-128066758-C-T is described in ClinVar as Benign. ClinVar VariationId is 1256715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 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.778-196C>T		intron	N/A	NP_037468.1	B3KNF6
	SEC61A1	NM_001400328.1		c.796-196C>T		intron	N/A	NP_001387257.1	B4DR61
	SEC61A1	NM_001400329.1		c.619-196C>T		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.778-196C>T		intron	N/A	ENSP00000243253.3	P61619-1
	SEC61A1	ENST00000483956.2	TSL:1	n.*268+55C>T		intron	N/A	ENSP00000514247.1	A0A8V8TNG8
	SEC61A1	ENST00000937479.1		c.905-196C>T		intron	N/A	ENSP00000607538.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11869 AN: 152020 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0889

GnomAD4 exome AF: 0.0968 AC: 42385 AN: 437750 Hom.: 2290 Cov.: 4 AF XY: 0.0968 AC XY: 22267 AN XY: 229984

African (AFR) AF: 0.0240 AC: 290 AN: 12068

American (AMR) AF: 0.0568 AC: 967 AN: 17022

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 1166 AN: 13282

East Asian (EAS) AF: 0.0113 AC: 342 AN: 30230

South Asian (SAS) AF: 0.0947 AC: 3964 AN: 41844

European-Finnish (FIN) AF: 0.0727 AC: 2428 AN: 33402

Middle Eastern (MID) AF: 0.109 AC: 209 AN: 1916

European-Non Finnish (NFE) AF: 0.117 AC: 30623 AN: 262662

Other (OTH) AF: 0.0946 AC: 2396 AN: 25324

GnomAD4 genome AF: 0.0780 AC: 11863 AN: 152138 Hom.: 582 Cov.: 32 AF XY: 0.0740 AC XY: 5505 AN XY: 74352

African (AFR) AF: 0.0259 AC: 1076 AN: 41530

American (AMR) AF: 0.0623 AC: 952 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5182

South Asian (SAS) AF: 0.0926 AC: 446 AN: 4816

European-Finnish (FIN) AF: 0.0634 AC: 670 AN: 10570

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7971 AN: 67978

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0962 Hom.: 237

Bravo AF: 0.0761

Asia WGS AF: 0.0540 AC: 186 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	-0.88
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.56
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: rs11714729; hg19: chr3-127785601;