9-99222618-G-T

Variant names:

• chr9-99222618-G-T
• rs572201993
• NM_006808.3:c.76G>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 12/19 in silico tools predict 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: 0.0000057 (0 hom.)
• Consequence: SEC61B NM_006808.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -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	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 4	ENST00000223641.5	NP_006799.1
SEC61B	XM_047422662.1	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	Appris	UniProt
SEC61B	ENST00000223641.5	c.76G>T	p.Ala26Ser	missense_variant	Exon 2 of 4	1	NM_006808.3	ENSP00000223641.4
SEC61B	ENST00000498603	c.-87G>T		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000474122.1
SEC61B	ENST00000481573.1	n.125G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000655 AC: 1 AN: 152572 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 80996

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 SAS 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: 8 AN: 1398382 Hom.: 0 Cov.: 31 AF XY: 0.00000435 AC XY: 3 AN XY: 690126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.053
Sift	Benign	0.48	T
Sift4G	Benign	0.40	T
Polyphen		0.018	B
Vest4		0.42
MutPred		0.31		Gain of phosphorylation at A26 (P = 0.0092);
MVP		0.36
MPC		0.49
ClinPred		0.98	D
GERP RS		3.4
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.7
Varity_R		0.088
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs572201993; hg19: chr9-101984900;