NM_018144.4:c.435C>T

Variant names:

• chr10-12149934-C-T
• rs10466280
• NM_018144.4:c.435C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018144.4(SEC61A2):​c.435C>T​(p.Ala145Ala) 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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.02).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61A2	NM_018144.4	MANE Select	c.435C>T	p.Ala145Ala	synonymous	Exon 6 of 12	NP_060614.2
	SEC61A2	NM_001142628.1		c.369C>T	p.Ala123Ala	synonymous	Exon 5 of 11	NP_001136100.1
	SEC61A2	NM_001142627.3		c.435C>T	p.Ala145Ala	synonymous	Exon 6 of 12	NP_001136099.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61A2	ENST00000298428.14	TSL:1 MANE Select	c.435C>T	p.Ala145Ala	synonymous	Exon 6 of 12	ENSP00000298428.9
	SEC61A2	ENST00000475268.5	TSL:1	n.435C>T		non_coding_transcript_exon	Exon 6 of 13	ENSP00000436749.1
	SEC61A2	ENST00000379033.7	TSL:2	c.369C>T	p.Ala123Ala	synonymous	Exon 5 of 11	ENSP00000368319.3

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

GnomAD2 exomes AF: 0.420 AC: 105402 AN: 251200 AF XY: 0.410

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 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

African (AFR) AF: 0.415 AC: 13877 AN: 33402

American (AMR) AF: 0.466 AC: 20838 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10882 AN: 26090

East Asian (EAS) AF: 0.518 AC: 20550 AN: 39672

South Asian (SAS) AF: 0.306 AC: 26332 AN: 86140

European-Finnish (FIN) AF: 0.379 AC: 20238 AN: 53390

Middle Eastern (MID) AF: 0.356 AC: 2053 AN: 5760

European-Non Finnish (NFE) AF: 0.425 AC: 471623 AN: 1108422

Other (OTH) AF: 0.411 AC: 24787 AN: 60246

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

African (AFR) AF: 0.420 AC: 17377 AN: 41402

American (AMR) AF: 0.405 AC: 6186 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2724 AN: 5172

South Asian (SAS) AF: 0.319 AC: 1531 AN: 4806

European-Finnish (FIN) AF: 0.381 AC: 4023 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.428 AC: 29102 AN: 67956

Other (OTH) AF: 0.406 AC: 857 AN: 2110

Alfa AF: 0.424 Hom.: 49416

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.0
DANN	Benign	0.79
PhyloP100		0.11
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	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: rs10466280; hg19: chr10-12191933; COSMIC: COSV53654055; COSMIC: COSV53654055;