dbSNP rs148757384: SEL1L:p.Gly306Cys (chr14-81498470-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005065.6(SEL1L):c.916G>T(p.Gly306Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SEL1L
NM_005065.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

SEL1L (HGNC:10717): (SEL1L adaptor subunit of SYVN1 ubiquitin ligase) The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SEL1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEL1L	NM_005065.6 link	c.916G>T	p.Gly306Cys	missense_variant	Exon 9 of 21	ENST00000336735.9	NP_005056.3	Q9UBV2-1Q3ZCU6
SEL1L	XM_005267988.4 link	c.853G>T	p.Gly285Cys	missense_variant	Exon 9 of 21		XP_005268045.1
SEL1L	XM_005267989.5 link	c.916G>T	p.Gly306Cys	missense_variant	Exon 9 of 20		XP_005268046.1
SEL1L	XM_047431676.1 link	c.853G>T	p.Gly285Cys	missense_variant	Exon 9 of 20		XP_047287632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEL1L	ENST00000336735.9 link	c.916G>T	p.Gly306Cys	missense_variant	Exon 9 of 21	1	NM_005065.6	ENSP00000337053.4		Q9UBV2-1
SEL1L	ENST00000554744.1 link	n.490G>T		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251340

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135842

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727156

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.37

MutationAssessor

Pathogenic

2.9

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.89

MutPred

0.63

Gain of helix (P = 0.062);

MVP

0.62

MPC

1.3

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.81

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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