dbSNP rs913079679: SEL1L3:p.Arg1051Gln (chr4-25757722-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015187.5(SEL1L3):c.3152G>A(p.Arg1051Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,598,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SEL1L3
NM_015187.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.3152G>A	p.Arg1051Gln	missense	Exon 22 of 24	NP_056002.2	Q68CR1-1
SEL1L3	NM_001297592.2		c.3047G>A	p.Arg1016Gln	missense	Exon 22 of 24	NP_001284521.1	Q68CR1-2
SEL1L3	NM_001297594.2		c.2693G>A	p.Arg898Gln	missense	Exon 22 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.3152G>A	p.Arg1051Gln	missense	Exon 22 of 24	ENSP00000382767.3	Q68CR1-1
SEL1L3	ENST00000264868.9	TSL:1	c.3047G>A	p.Arg1016Gln	missense	Exon 22 of 24	ENSP00000264868.5	Q68CR1-2
SEL1L3	ENST00000929301.1		c.3257G>A	p.Arg1086Gln	missense	Exon 22 of 24	ENSP00000599360.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000447

AC:

AN:

223916

AF XY:

0.00000829

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000996

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1446024

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

717508

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33212

American (AMR)

AF:

0.0000235

AC:

AN:

42552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

38940

South Asian (SAS)

AF:

0.00

AC:

AN:

83070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1104580

Other (OTH)

AF:

0.00

AC:

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000197

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

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:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

3.4

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.59

REVEL

Benign

0.14

Sift

Benign

0.28

Sift4G

Pathogenic

0.0

Polyphen

0.82

Vest4

0.67

MutPred

0.55

Loss of methylation at R1051 (P = 0.0289)

MVP

0.043

MPC

0.63

ClinPred

0.73

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.38

Mutation Taster

=86/14

polymorphism

(source)

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

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