rs148143457

Variant names:

• chr9-99227928-C-T
• rs148143457
• NM_006808.3:c.131C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006808.3(SEC61B):​c.131C>T​(p.Ala44Val) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,613,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: SEC61B NM_006808.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017097324).
• BS2: High AC in GnomAd4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61B	NM_006808.3	MANE Select	c.131C>T	p.Ala44Val	missense	Exon 3 of 4	NP_006799.1	P60468

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC61B	ENST00000223641.5	TSL:1 MANE Select	c.131C>T	p.Ala44Val	missense	Exon 3 of 4	ENSP00000223641.4	P60468
	SEC61B	ENST00000498603.5	TSL:3	c.-32C>T		5_prime_UTR	Exon 3 of 4	ENSP00000474122.1	S4R3B5
	SEC61B	ENST00000926713.1		c.102-2409C>T		intron	N/A	ENSP00000596772.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 251150 AF XY: 0.000243

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000128 AC: 187 AN: 1461758 Hom.: 1 Cov.: 31 AF XY: 0.000122 AC XY: 89 AN XY: 727192

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00509 AC: 133 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111942

Other (OTH) AF: 0.000414 AC: 25 AN: 60384

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74306

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000286 Hom.: 1

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.85	T
PhyloP100		4.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.030
Sift	Benign	0.054	T
Sift4G	Benign	0.20	T
Polyphen		0.043	B
Vest4		0.62
MVP		0.36
MPC		0.53
ClinPred		0.091	T
GERP RS		4.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.19
gMVP		0.66
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs148143457; hg19: chr9-101990210;