Genetic Variant SEC61B:p.Ala26Ser (chr9-99222618-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006808.3(SEC61B):c.76G>T(p.Ala26Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000572 in 1,398,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SEC61B
NM_006808.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.73

Publications

1 publications found

Variant links:

Genes affected

SEC61B (HGNC:16993): (SEC61 translocon subunit beta) The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the beta-subunit protein. The Sec61 subunits are also observed in the post-ER compartment, suggesting that these proteins can escape the ER and recycle back. There is evidence for multiple polyadenylated sites for this transcript. [provided by RefSeq, Jul 2008]

SEC61B Gene-Disease associations (from GenCC):

polycystic liver disease 1
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
SEC61B-related polycystic liver disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SEC61B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18185869).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61B	NM_006808.3 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 4	ENST00000223641.5	NP_006799.1	P60468
SEC61B	XM_047422662.1 link	c.-1499G>T		5_prime_UTR_variant	Exon 1 of 3		XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC61B	ENST00000223641.5 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 4	1	NM_006808.3	ENSP00000223641.4	P60468
SEC61B	ENST00000481573.1 link	n.125G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
SEC61B	ENST00000498603.5 link	c.-87G>T		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000474122.1	S4R3B5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000655

AC:

AN:

152572

AF XY:

0.00

show subpopulations

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:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1398382

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31624

American (AMR)

AF:

0.00

AC:

AN:

35596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25056

East Asian (EAS)

AF:

0.00

AC:

AN:

35816

South Asian (SAS)

AF:

0.00

AC:

AN:

79532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000741

AC:

AN:

1079242

Other (OTH)

AF:

0.00

AC:

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.049

Eigen

Benign

-0.11

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.86

M_CAP

Benign

0.0086

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

PhyloP100

4.7

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.080

REVEL

Benign

0.053

Sift

Benign

0.48

Sift4G

Benign

0.40

Polyphen

0.018

Vest4

0.42

MutPred

0.31

Gain of phosphorylation at A26 (P = 0.0092);

MVP

0.36

MPC

0.49

ClinPred

0.98

GERP RS

3.4

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.7

Varity_R

0.088

gMVP

0.52

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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9-99222618-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over