Variant 4-25757712-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015187.5(SEL1L3):c.3162G>C(p.Trp1054Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,596,134 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0030 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 93 hom. )

Consequence

SEL1L3
NM_015187.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.31

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00390023).

BP6

Variant 4-25757712-C-G is Benign according to our data. Variant chr4-25757712-C-G is described in ClinVar as [Benign]. Clinvar id is 771359.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L3	NM_015187.5 linkuse as main transcript	c.3162G>C	p.Trp1054Cys	missense_variant	22/24	ENST00000399878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L3	ENST00000399878.8 linkuse as main transcript	c.3162G>C	p.Trp1054Cys	missense_variant	22/24	1	NM_015187.5	P1	Q68CR1-1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0567

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00643

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00536

AC:

1181

AN:

220466

Hom.:

AF XY:

0.00494

AC XY:

588

AN XY:

118914

show subpopulations

Gnomad AFR exome

AF:

0.000234

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00202

Gnomad EAS exome

AF:

0.0559

Gnomad SAS exome

AF:

0.000896

Gnomad FIN exome

AF:

0.00608

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00246

AC:

3548

AN:

1444026

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1724

AN XY:

716400

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.0662

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00664

Gnomad4 NFE exome

AF:

0.000122

Gnomad4 OTH exome

AF:

0.00395

GnomAD4 genome

AF:

0.00304

AC:

463

AN:

152108

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

263

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0568

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00643

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00304

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.00430

AC:

519

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.28

T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.086

Sift

Benign

0.080

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0090

B;.;.

Vest4

0.48

MutPred

0.32

Gain of loop (P = 0.0195);.;.;

MVP

0.068

MPC

0.29

ClinPred

0.027

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.76

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