10-88914588-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_020799.4(STAMBPL1):ā€‹c.833A>Gā€‹(p.Lys278Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,540,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000086 ( 0 hom., cov: 32)
Exomes š‘“: 0.00024 ( 0 hom. )

Consequence

STAMBPL1
NM_020799.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.575
Variant links:
Genes affected
STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09835857).
BP6
Variant 10-88914588-A-G is Benign according to our data. Variant chr10-88914588-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3170923.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STAMBPL1NM_020799.4 linkuse as main transcriptc.833A>G p.Lys278Arg missense_variant 7/11 ENST00000371926.8 NP_065850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STAMBPL1ENST00000371926.8 linkuse as main transcriptc.833A>G p.Lys278Arg missense_variant 7/111 NM_020799.4 ENSP00000360994 P1Q96FJ0-1
STAMBPL1ENST00000371924.5 linkuse as main transcriptc.833A>G p.Lys278Arg missense_variant 6/101 ENSP00000360992 P1Q96FJ0-1
STAMBPL1ENST00000371927.7 linkuse as main transcriptc.833A>G p.Lys278Arg missense_variant 7/112 ENSP00000360995 Q96FJ0-2
STAMBPL1ENST00000371922.1 linkuse as main transcriptn.1158A>G non_coding_transcript_exon_variant 2/62

Frequencies

GnomAD3 genomes
AF:
0.0000857
AC:
13
AN:
151746
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000329
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:
0.0000736
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000421
AC:
9
AN:
213840
Hom.:
0
AF XY:
0.0000598
AC XY:
7
AN XY:
117066
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 SAS exome
AF:
0.0000381
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000238
AC:
331
AN:
1388298
Hom.:
0
Cov.:
30
AF XY:
0.000230
AC XY:
159
AN XY:
689844
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000133
Gnomad4 FIN exome
AF:
0.0000588
Gnomad4 NFE exome
AF:
0.000297
Gnomad4 OTH exome
AF:
0.000106
GnomAD4 genome
AF:
0.0000857
AC:
13
AN:
151746
Hom.:
0
Cov.:
32
AF XY:
0.0000809
AC XY:
6
AN XY:
74140
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000329
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000968
Hom.:
0
Bravo
AF:
0.000132
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 30, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
2.8
DANN
Benign
0.88
DEOGEN2
Benign
0.0058
T;.;T;.
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.48
T;T;.;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.098
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.040
N;N;N;.
MutationTaster
Benign
0.94
N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.44
N;N;N;N
REVEL
Benign
0.086
Sift
Benign
0.71
T;T;T;T
Sift4G
Benign
0.48
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.21
MVP
0.43
MPC
0.059
ClinPred
0.018
T
GERP RS
-3.7
Varity_R
0.083
gMVP
0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373894376; hg19: chr10-90674345; API