rs10466280

chr10-12149934-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018144.4(SEC61A2):c.435C>T(p.Ala145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,609,740 control chromosomes in the GnomAD database, including 143,413 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 0.42 (13356 hom., cov: 32)
  • Exomes 𝑓: 0.42 (130057 hom.)
• Consequence: SEC61A2 NM_018144.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

Genes affected

SEC61A2 (HGNC:17702): (SEC61 translocon subunit alpha 2) The protein encoded by this gene has similarity to a mouse protein which suggests a role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. It may also be required for the assembly of membrane and secretory proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC61A2	NM_018144.4	c.435C>T	p.Ala145=	synonymous_variant	6/12	ENST00000298428.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC61A2	ENST00000298428.14	c.435C>T	p.Ala145=	synonymous_variant	6/12	1	NM_018144.4	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63658 AN: 151820 Hom.: 13351 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.411

GnomAD3 exomes AF: 0.420 AC: 105402 AN: 251200 Hom.: 22648 AF XY: 0.410 AC XY: 55713 AN XY: 135778

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.537

Gnomad SAS exome AF: 0.304

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.419 AC: 611180 AN: 1457802 Hom.: 130057 Cov.: 32 AF XY: 0.416 AC XY: 301611 AN XY: 725488

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.419 AC: 63679 AN: 151938 Hom.: 13356 Cov.: 32 AF XY: 0.414 AC XY: 30722 AN XY: 74250

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.406

Alfa AF: 0.423 Hom.: 32163

Bravo AF: 0.427

Asia WGS AF: 0.364 AC: 1266 AN: 3478

EpiCase AF: 0.414

EpiControl AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	4.0
Dann	Benign	0.79
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

Publications

LitVar

Other links and lift over

dbSNP: rs10466280; hg19: chr10-12191933; COSMIC: COSV53654055; COSMIC: COSV53654055;