GeneBe

NM_003900.5:c.954C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003900.5(SQSTM1):​c.954C>G​(p.Ser318Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S318S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SQSTM1
NM_003900.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.75

Publications

0 publications found
Variant links:
Genes affected
SQSTM1 (HGNC:11280): (sequestosome 1) This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]
SQSTM1 Gene-Disease associations (from GenCC):
  • neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
  • frontotemporal dementia and/or amyotrophic lateral sclerosis 3
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
  • osteosarcoma
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • Paget disease of bone 3
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • behavioral variant of frontotemporal dementia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • frontotemporal dementia with motor neuron disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP7
Synonymous conserved (PhyloP=-5.75 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SQSTM1NM_003900.5 linkc.954C>G p.Ser318Ser synonymous_variant Exon 6 of 8 ENST00000389805.9 NP_003891.1 Q13501-1
SQSTM1NM_001142298.2 linkc.702C>G p.Ser234Ser synonymous_variant Exon 7 of 9 NP_001135770.1 Q13501-2
SQSTM1NM_001142299.2 linkc.702C>G p.Ser234Ser synonymous_variant Exon 7 of 9 NP_001135771.1 Q13501-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SQSTM1ENST00000389805.9 linkc.954C>G p.Ser318Ser synonymous_variant Exon 6 of 8 1 NM_003900.5 ENSP00000374455.4 Q13501-1
SQSTM1ENST00000360718.5 linkc.702C>G p.Ser234Ser synonymous_variant Exon 5 of 7 1 ENSP00000353944.5 Q13501-2
SQSTM1ENST00000466342.1 linkn.653C>G non_coding_transcript_exon_variant Exon 4 of 4 2
SQSTM1ENST00000510187.5 linkc.950+4C>G splice_region_variant, intron_variant Intron 6 of 6 5 ENSP00000424477.1 E7EMC7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1436432
Hom.:
0
Cov.:
36
AF XY:
0.00000140
AC XY:
1
AN XY:
712920
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32966
American (AMR)
AF:
0.00
AC:
0
AN:
40728
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25738
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38288
South Asian (SAS)
AF:
0.0000119
AC:
1
AN:
84098
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47990
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5086
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1102126
Other (OTH)
AF:
0.00
AC:
0
AN:
59412
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.035
DANN
Benign
0.74
PhyloP100
-5.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs56092424; hg19: chr5-179260231; API