10-88913267-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020799.4(STAMBPL1):​c.587G>A​(p.Ser196Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,812 control chromosomes in the GnomAD database, including 16,044 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1420 hom., cov: 32)
Exomes 𝑓: 0.14 ( 14624 hom. )

Consequence

STAMBPL1
NM_020799.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

20 publications found
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0011698604).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAMBPL1NM_020799.4 linkc.587G>A p.Ser196Asn missense_variant Exon 6 of 11 ENST00000371926.8 NP_065850.1 Q96FJ0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAMBPL1ENST00000371926.8 linkc.587G>A p.Ser196Asn missense_variant Exon 6 of 11 1 NM_020799.4 ENSP00000360994.3 Q96FJ0-1
STAMBPL1ENST00000371924.5 linkc.587G>A p.Ser196Asn missense_variant Exon 5 of 10 1 ENSP00000360992.1 Q96FJ0-1
STAMBPL1ENST00000371927.7 linkc.587G>A p.Ser196Asn missense_variant Exon 6 of 11 2 ENSP00000360995.3 Q96FJ0-2
STAMBPL1ENST00000371922.1 linkn.912G>A non_coding_transcript_exon_variant Exon 1 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19670
AN:
152114
Hom.:
1417
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.154
Gnomad AMI
AF:
0.0866
Gnomad AMR
AF:
0.111
Gnomad ASJ
AF:
0.0840
Gnomad EAS
AF:
0.00211
Gnomad SAS
AF:
0.0722
Gnomad FIN
AF:
0.0738
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.145
Gnomad OTH
AF:
0.103
GnomAD2 exomes
AF:
0.108
AC:
26962
AN:
250718
AF XY:
0.107
show subpopulations
Gnomad AFR exome
AF:
0.154
Gnomad AMR exome
AF:
0.0824
Gnomad ASJ exome
AF:
0.0875
Gnomad EAS exome
AF:
0.00142
Gnomad FIN exome
AF:
0.0719
Gnomad NFE exome
AF:
0.144
Gnomad OTH exome
AF:
0.111
GnomAD4 exome
AF:
0.137
AC:
199841
AN:
1461580
Hom.:
14624
Cov.:
31
AF XY:
0.135
AC XY:
97897
AN XY:
727094
show subpopulations
African (AFR)
AF:
0.155
AC:
5176
AN:
33448
American (AMR)
AF:
0.0859
AC:
3836
AN:
44672
Ashkenazi Jewish (ASJ)
AF:
0.0875
AC:
2286
AN:
26124
East Asian (EAS)
AF:
0.000605
AC:
24
AN:
39688
South Asian (SAS)
AF:
0.0745
AC:
6424
AN:
86250
European-Finnish (FIN)
AF:
0.0785
AC:
4195
AN:
53416
Middle Eastern (MID)
AF:
0.0932
AC:
537
AN:
5762
European-Non Finnish (NFE)
AF:
0.152
AC:
169532
AN:
1111840
Other (OTH)
AF:
0.130
AC:
7831
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
10899
21798
32698
43597
54496
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5950
11900
17850
23800
29750
<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:
0.129
AC:
19688
AN:
152232
Hom.:
1420
Cov.:
32
AF XY:
0.123
AC XY:
9183
AN XY:
74432
show subpopulations
African (AFR)
AF:
0.154
AC:
6392
AN:
41530
American (AMR)
AF:
0.111
AC:
1701
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.0840
AC:
291
AN:
3466
East Asian (EAS)
AF:
0.00212
AC:
11
AN:
5190
South Asian (SAS)
AF:
0.0714
AC:
345
AN:
4830
European-Finnish (FIN)
AF:
0.0738
AC:
783
AN:
10610
Middle Eastern (MID)
AF:
0.0544
AC:
16
AN:
294
European-Non Finnish (NFE)
AF:
0.145
AC:
9854
AN:
68002
Other (OTH)
AF:
0.102
AC:
216
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
867
1734
2602
3469
4336
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
220
440
660
880
1100
<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:
0.138
Hom.:
5338
Bravo
AF:
0.133
ESP6500AA
AF:
0.160
AC:
705
ESP6500EA
AF:
0.143
AC:
1228
ExAC
AF:
0.111
AC:
13479
Asia WGS
AF:
0.0410
AC:
144
AN:
3478
EpiCase
AF:
0.146
EpiControl
AF:
0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.77
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.0045
T;.;T;.
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.59
T;T;.;T
MetaRNN
Benign
0.0012
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.71
N;N;N;.
PhyloP100
1.3
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.0
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.49
T;T;T;T
Sift4G
Benign
0.51
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.029
MPC
0.066
ClinPred
0.0017
T
GERP RS
3.9
Varity_R
0.042
gMVP
0.28
Mutation Taster
=97/3
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs12254856; hg19: chr10-90673024; COSMIC: COSV64222745; API