Variant chr14-81487440-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005065.6(SEL1L):c.1582A>G(p.Met528Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,264 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SEL1L
NM_005065.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEL1L	NM_005065.6 linkuse as main transcript	c.1582A>G	p.Met528Val	missense_variant	16/21	ENST00000336735.9	NP_005056.3	Q9UBV2-1Q3ZCU6
SEL1L	XM_005267988.4 linkuse as main transcript	c.1519A>G	p.Met507Val	missense_variant	16/21		XP_005268045.1
SEL1L	XM_005267989.5 linkuse as main transcript	c.1513A>G	p.Met505Val	missense_variant	15/20		XP_005268046.1
SEL1L	XM_047431676.1 linkuse as main transcript	c.1450A>G	p.Met484Val	missense_variant	15/20		XP_047287632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEL1L	ENST00000336735.9 linkuse as main transcript	c.1582A>G	p.Met528Val	missense_variant	16/21	1	NM_005065.6	ENSP00000337053.4		Q9UBV2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453264

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722906

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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

Nov 11, 2024

The c.1582A>G (p.M528V) alteration is located in exon 1 (coding exon 1) of the SEL1L gene. This alteration results from a A to G substitution at nucleotide position 1582, causing the methionine (M) at amino acid position 528 to be replaced by a valine (V). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.30

MutationAssessor

Pathogenic

3.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.48

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.010

Polyphen

0.94

Vest4

0.83

MutPred

0.46

Loss of disorder (P = 0.1041);

MVP

0.69

MPC

1.2

ClinPred

0.96

GERP RS

5.1

Varity_R

0.62

gMVP

0.85

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over