chr10-88910920-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020799.4(STAMBPL1):ā€‹c.329T>Cā€‹(p.Leu110Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,430,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000077 ( 0 hom. )

Consequence

STAMBPL1
NM_020799.4 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.55
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STAMBPL1NM_020799.4 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 5/11 ENST00000371926.8 NP_065850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STAMBPL1ENST00000371926.8 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 5/111 NM_020799.4 ENSP00000360994 P1Q96FJ0-1
STAMBPL1ENST00000371924.5 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 4/101 ENSP00000360992 P1Q96FJ0-1
STAMBPL1ENST00000371927.7 linkuse as main transcriptc.329T>C p.Leu110Pro missense_variant 5/112 ENSP00000360995 Q96FJ0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000769
AC:
11
AN:
1430082
Hom.:
0
Cov.:
28
AF XY:
0.00000844
AC XY:
6
AN XY:
710696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000818
Gnomad4 OTH exome
AF:
0.0000338
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 09, 2024The c.329T>C (p.L110P) alteration is located in exon 5 (coding exon 4) of the STAMBPL1 gene. This alteration results from a T to C substitution at nucleotide position 329, causing the leucine (L) at amino acid position 110 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.80
D;.;D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D;.
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.90
D;D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.9
M;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-5.5
D;D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.95
MutPred
0.71
Gain of loop (P = 0.002);Gain of loop (P = 0.002);Gain of loop (P = 0.002);
MVP
0.60
MPC
0.52
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.95
gMVP
0.85

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: rs1845206120; hg19: chr10-90670677; API