Variant 4-25804723-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015187.5(SEL1L3):c.1594G>C(p.Glu532Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,628 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 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

SEL1L3
NM_015187.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

SEL1L3 (HGNC:29108): (SEL1L family member 3) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SEL1L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12555185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L3	NM_015187.5 linkuse as main transcript	c.1594G>C	p.Glu532Gln	missense_variant	10/24	ENST00000399878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L3	ENST00000399878.8 linkuse as main transcript	c.1594G>C	p.Glu532Gln	missense_variant	10/24	1	NM_015187.5	P1	Q68CR1-1
SEL1L3	ENST00000264868.9 linkuse as main transcript	c.1489G>C	p.Glu497Gln	missense_variant	10/24	1			Q68CR1-2
SEL1L3	ENST00000502949.5 linkuse as main transcript	c.1135G>C	p.Glu379Gln	missense_variant	10/24	2			Q68CR1-3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000136

AC:

AN:

249174

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000239

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000318

AC:

465

AN:

1461306

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

206

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000399

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000171

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

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

Mar 01, 2023

The c.1594G>C (p.E532Q) alteration is located in exon 10 (coding exon 10) of the SEL1L3 gene. This alteration results from a G to C substitution at nucleotide position 1594, causing the glutamic acid (E) at amino acid position 532 to be replaced by a glutamine (Q). 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

0.098

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

0.0031

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.92

N;N;N

REVEL

Benign

0.076

Sift

Benign

0.053

T;T;T

Sift4G

Benign

0.087

T;T;T

Polyphen

0.41

B;.;.

Vest4

0.30

MVP

0.15

MPC

0.36

ClinPred

0.059

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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