Variant 10-12149934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

SEC61A2 (HGNC:):

SEC61A2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SEC61A2	NM_018144.4 linkuse as main transcript	c.435C>T	p.Ala145Ala	synonymous_variant	6/12	ENST00000298428.14	NP_060614.2	Q9H9S3-1Q8TC24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC61A2	ENST00000298428.14 linkuse as main transcript	c.435C>T	p.Ala145Ala	synonymous_variant	6/12	1	NM_018144.4	ENSP00000298428.9		Q9H9S3-1

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

GnomAD3 exomes

AF:

0.420

AC:

105402

AN:

251200

Hom.:

22648

AF XY:

0.410

AC XY:

55713

AN XY:

135778

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 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.:

AF XY:

0.416

AC XY:

301611

AN XY:

725488

show subpopulations

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.:

AF XY:

0.414

AC XY:

30722

AN XY:

74250

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over