Variant 10-88913174-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020799.4(STAMBPL1):c.494C>T(p.Ala165Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,430 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

STAMBPL1
NM_020799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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]

STAMBPL1 links:

STAMBPL1 (HGNC:):

STAMBPL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18017909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBPL1	NM_020799.4 linkuse as main transcript	c.494C>T	p.Ala165Val	missense_variant	6/11	ENST00000371926.8	NP_065850.1	Q96FJ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STAMBPL1	ENST00000371926.8 linkuse as main transcript	c.494C>T	p.Ala165Val	missense_variant	6/11	1	NM_020799.4	ENSP00000360994.3	Q96FJ0-1
STAMBPL1	ENST00000371924.5 linkuse as main transcript	c.494C>T	p.Ala165Val	missense_variant	5/10	1		ENSP00000360992.1	Q96FJ0-1
STAMBPL1	ENST00000371927.7 linkuse as main transcript	c.494C>T	p.Ala165Val	missense_variant	6/11	2		ENSP00000360995.3	Q96FJ0-2
STAMBPL1	ENST00000371922.1 linkuse as main transcript	n.819C>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250570

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000958

AC:

AN:

1461430

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

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 submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.494C>T (p.A165V) alteration is located in exon 6 (coding exon 5) of the STAMBPL1 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the alanine (A) at amino acid position 165 to be replaced by a valine (V). 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

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

T;.;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.072

T;D;T

Sift4G

Benign

0.24

T;T;T

Polyphen

1.0

D;P;D

Vest4

0.23

MutPred

0.35

Loss of ubiquitination at K162 (P = 0.0692);Loss of ubiquitination at K162 (P = 0.0692);Loss of ubiquitination at K162 (P = 0.0692);

MVP

0.51

MPC

0.42

ClinPred

0.33

GERP RS

6.0

Varity_R

0.22

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over