dbSNP rs138960171: SS18L1:p.Val130Met (chr20-62162763-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001301778.2(SS18L1):c.-6G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000416 in 1,608,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SS18L1
NM_001301778.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Publications

0 publications found

Variant links:

Genes affected

SS18L1 (HGNC:15592): (SS18L1 subunit of BAF chromatin remodeling complex) This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SS18L1 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Genomics England PanelApp

SS18L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11696735).

BS2

High AC in GnomAd4 at 29 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301778.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SS18L1	NM_198935.3	MANE Select	c.388G>A	p.Val130Met	missense	Exon 5 of 11	NP_945173.1	O75177-1
SS18L1	NM_001301778.2		c.-6G>A		5_prime_UTR_premature_start_codon_gain	Exon 6 of 12	NP_001288707.1	O75177-4
SS18L1	NM_001301778.2		c.-6G>A		5_prime_UTR	Exon 6 of 12	NP_001288707.1	O75177-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SS18L1	ENST00000331758.8	TSL:1 MANE Select	c.388G>A	p.Val130Met	missense	Exon 5 of 11	ENSP00000333012.3	O75177-1
SS18L1	ENST00000370848.8	TSL:1	c.142G>A	p.Val48Met	missense	Exon 2 of 9	ENSP00000359885.5	O75177-3
SS18L1	ENST00000491916.1	TSL:2	n.216G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000324

AC:

AN:

247090

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.000506

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1456448

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

723764

show subpopulations

African (AFR)

AF:

0.000419

AC:

AN:

33378

American (AMR)

AF:

0.0000449

AC:

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.00

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52068

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1108880

Other (OTH)

AF:

0.0000665

AC:

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.000191

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

41454

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000339

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

M_CAP

Benign

0.029

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.66

PhyloP100

5.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.050

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.31

MVP

0.46

MPC

1.2

ClinPred

0.10

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.091

gMVP

0.29

Mutation Taster

=84/16

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