Variant 4-25790562-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015187.5(SEL1L3):c.1969A>G(p.Thr657Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 1,608,042 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 30)

Exomes 𝑓: 0.00038 ( 3 hom. )

Consequence

SEL1L3
NM_015187.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.766

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059874356).

BP6

Variant 4-25790562-T-C is Benign according to our data. Variant chr4-25790562-T-C is described in ClinVar as [Benign]. Clinvar id is 783419.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L3	NM_015187.5 linkuse as main transcript	c.1969A>G	p.Thr657Ala	missense_variant	12/24	ENST00000399878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L3	ENST00000399878.8 linkuse as main transcript	c.1969A>G	p.Thr657Ala	missense_variant	12/24	1	NM_015187.5	P1	Q68CR1-1
SEL1L3	ENST00000264868.9 linkuse as main transcript	c.1864A>G	p.Thr622Ala	missense_variant	12/24	1			Q68CR1-2
SEL1L3	ENST00000502949.5 linkuse as main transcript	c.1510A>G	p.Thr504Ala	missense_variant	12/24	2			Q68CR1-3

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

562

AN:

150752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00173

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:

0.0000147

Gnomad OTH

AF:

0.00341

GnomAD3 exomes

AF:

0.000847

AC:

210

AN:

247904

Hom.:

AF XY:

0.000654

AC XY:

AN XY:

134600

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000234

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:

0.0000534

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000375

AC:

547

AN:

1457172

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

233

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.000336

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:

0.0000289

Gnomad4 OTH exome

AF:

0.000698

GnomAD4 genome

AF:

0.00373

AC:

562

AN:

150870

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

271

AN XY:

73592

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00173

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00337

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00421

ESP6500AA

AF:

0.0128

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00107

AC:

129

Asia WGS

AF:

0.000289

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

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.0086

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.080

N;.;.

MutationTaster

Benign

0.57

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.46

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.27

MVP

0.043

MPC

0.18

ClinPred

0.0070

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.46

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