Variant 14-81504204-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005065.6(SEL1L):c.611G>A(p.Arg204Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,583,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SEL1L
NM_005065.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04263112).

BS2

High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L	NM_005065.6 linkuse as main transcript	c.611G>A	p.Arg204Lys	missense_variant	5/21	ENST00000336735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L	ENST00000336735.9 linkuse as main transcript	c.611G>A	p.Arg204Lys	missense_variant	5/21	1	NM_005065.6	P1	Q9UBV2-1
SEL1L	ENST00000555824.5 linkuse as main transcript	c.611G>A	p.Arg204Lys	missense_variant	5/8	1			Q9UBV2-2
SEL1L	ENST00000554744.1 linkuse as main transcript	n.185G>A		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000125

AC:

AN:

231644

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

125942

show subpopulations

Gnomad AFR exome

AF:

0.0000689

Gnomad AMR exome

AF:

0.0000683

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:

0.000223

Gnomad OTH exome

AF:

0.000369

GnomAD4 exome

AF:

0.000270

AC:

387

AN:

1431350

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

169

AN XY:

712492

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.0000740

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:

0.000345

Gnomad4 OTH exome

AF:

0.0000849

GnomAD4 genome

AF:

0.000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.611G>A (p.R204K) alteration is located in exon 1 (coding exon 1) of the SEL1L gene. This alteration results from a G to A substitution at nucleotide position 611, causing the arginine (R) at amino acid position 204 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.69

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.092

Sift

Benign

0.92

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.16

MVP

0.12

MPC

0.42

ClinPred

0.047

GERP RS

4.8

Varity_R

0.059

gMVP

0.40

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over