Variant 10-88910988-T-C 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.397T>C(p.Tyr133His) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,439,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

STAMBPL1
NM_020799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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:

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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=0.16954711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBPL1	NM_020799.4 linkuse as main transcript	c.397T>C	p.Tyr133His	missense_variant	5/11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8 linkuse as main transcript	c.397T>C	p.Tyr133His	missense_variant	5/11	1	NM_020799.4	ENSP00000360994	P1	Q96FJ0-1
STAMBPL1	ENST00000371924.5 linkuse as main transcript	c.397T>C	p.Tyr133His	missense_variant	4/10	1		ENSP00000360992	P1	Q96FJ0-1
STAMBPL1	ENST00000371927.7 linkuse as main transcript	c.397T>C	p.Tyr133His	missense_variant	5/11	2		ENSP00000360995		Q96FJ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1439790

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715200

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:

0.00000362

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 06, 2024

The c.397T>C (p.Y133H) 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 397, causing the tyrosine (Y) at amino acid position 133 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

0.025

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;D;.

M_CAP

Benign

0.0070

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.35

MutPred

0.28

Loss of phosphorylation at Y133 (P = 0.0506);Loss of phosphorylation at Y133 (P = 0.0506);Loss of phosphorylation at Y133 (P = 0.0506);

MVP

0.28

MPC

0.090

ClinPred

0.69

GERP RS

5.8

Varity_R

0.14

gMVP

0.53

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