9-99222654-C-T

Variant names:

• chr9-99222654-C-T
• rs170623
• NM_006808.3:c.101+11C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006808.3(SEC61B):​c.101+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEC61B NM_006808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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.101+11C>T		intron	N/A	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.101+11C>T		intron	N/A	ENSP00000223641.4	P60468
	SEC61B	ENST00000926713.1		c.101+11C>T		intron	N/A	ENSP00000596772.1
	SEC61B	ENST00000498603.5	TSL:3	c.-62+11C>T		intron	N/A	ENSP00000474122.1	S4R3B5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000772 AC: 1 AN: 129562 AF XY: 0.00

Gnomad AFR exome AF: 0.000123

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1363984 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 671474

African (AFR) AF: 0.00 AC: 0 AN: 30532

American (AMR) AF: 0.00 AC: 0 AN: 31576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23442

East Asian (EAS) AF: 0.00 AC: 0 AN: 35380

South Asian (SAS) AF: 0.00 AC: 0 AN: 76064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061166

Other (OTH) AF: 0.00 AC: 0 AN: 56540

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.92
PhyloP100		-0.78
PromoterAI		0.013	Neutral

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: rs170623; hg19: chr9-101984936;