dbSNP rs746867162: SEL1L3:p.Pro1128Leu (chr4-25748441-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015187.5(SEL1L3):c.3383C>T(p.Pro1128Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,610,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SEL1L3
NM_015187.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.562

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032409698).

BP6

Variant 4-25748441-G-A is Benign according to our data. Variant chr4-25748441-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2300052.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015187.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEL1L3	NM_015187.5	MANE Select	c.3383C>T	p.Pro1128Leu	missense	Exon 24 of 24	NP_056002.2	Q68CR1-1
SEL1L3	NM_001297592.2		c.3278C>T	p.Pro1093Leu	missense	Exon 24 of 24	NP_001284521.1	Q68CR1-2
SEL1L3	NM_001297594.2		c.2924C>T	p.Pro975Leu	missense	Exon 24 of 24	NP_001284523.1	Q68CR1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEL1L3	ENST00000399878.8	TSL:1 MANE Select	c.3383C>T	p.Pro1128Leu	missense	Exon 24 of 24	ENSP00000382767.3	Q68CR1-1
SEL1L3	ENST00000264868.9	TSL:1	c.3278C>T	p.Pro1093Leu	missense	Exon 24 of 24	ENSP00000264868.5	Q68CR1-2
SEL1L3	ENST00000929301.1		c.3488C>T	p.Pro1163Leu	missense	Exon 24 of 24	ENSP00000599360.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

243022

AF XY:

0.0000228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1458202

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

724922

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33434

American (AMR)

AF:

0.0000227

AC:

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39608

South Asian (SAS)

AF:

0.000153

AC:

AN:

85178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1110572

Other (OTH)

AF:

0.0000332

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000501

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.3

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.67

M_CAP

Benign

0.0035

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PhyloP100

0.56

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.59

REVEL

Benign

0.054

Sift

Benign

0.061

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.079

MutPred

0.14

Loss of catalytic residue at P1128 (P = 0.0423)

MVP

0.043

MPC

0.19

ClinPred

0.025

GERP RS

0.14

Varity_R

0.017

gMVP

0.23

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over