dbSNP rs10466280: SEC61A2:p.Ala145Ala (chr10-12149934-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

Publications

26 publications found

Variant links:

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]

SEC61A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61A2	NM_018144.4 link	c.435C>T	p.Ala145Ala	synonymous_variant	Exon 6 of 12	ENST00000298428.14	NP_060614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61A2	ENST00000298428.14 link	c.435C>T	p.Ala145Ala	synonymous_variant	Exon 6 of 12	1	NM_018144.4	ENSP00000298428.9

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63658

AN:

151820

Hom.:

13351

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.416

AC XY:

301611

AN XY:

725488

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

16420

32839

49259

65678

82098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14426

28852

43278

57704

72130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.419

AC:

63679

AN:

151938

Hom.:

13356

Cov.:

AF XY:

0.414

AC XY:

30722

AN XY:

74250

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1911

3822

5734

7645

9556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.0

(source)

DANN

Benign

0.79

PhyloP100

0.11

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over