rs1240393119

Variant names:

• chr3-128064902-C-T
• rs1240393119
• NM_013336.4:c.642C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_013336.4(SEC61A1):​c.642C>T​(p.Ile214Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SEC61A1 NM_013336.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-128064902-C-T is Benign according to our data. Variant chr3-128064902-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1633996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

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.642C>T	p.Ile214Ile	synonymous	Exon 8 of 12	NP_037468.1	B3KNF6
	SEC61A1	NM_001400328.1		c.660C>T	p.Ile220Ile	synonymous	Exon 8 of 12	NP_001387257.1	B4DR61
	SEC61A1	NM_001400329.1		c.483C>T	p.Ile161Ile	synonymous	Exon 7 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.642C>T	p.Ile214Ile	synonymous	Exon 8 of 12	ENSP00000243253.3	P61619-1
	SEC61A1	ENST00000483956.2	TSL:1	n.642C>T		non_coding_transcript_exon	Exon 8 of 14	ENSP00000514247.1	A0A8V8TNG8
	SEC61A1	ENST00000937479.1		c.642C>T	p.Ile214Ile	synonymous	Exon 8 of 13	ENSP00000607538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 248942 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1458798 Hom.: 0 Cov.: 32 AF XY: 0.00000689 AC XY: 5 AN XY: 725454

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110242

Other (OTH) AF: 0.0000498 AC: 3 AN: 60284

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000314 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1240393119; hg19: chr3-127783745;