Variant 10-88913108-A-G 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.428A>G(p.Tyr143Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,438,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 3.99

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:

Genome browser will be placed here

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=0.09608656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAMBPL1	NM_020799.4 link	c.428A>G	p.Tyr143Cys	missense_variant	Exon 6 of 11	ENST00000371926.8	NP_065850.1	Q96FJ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STAMBPL1	ENST00000371926.8 link	c.428A>G	p.Tyr143Cys	missense_variant	Exon 6 of 11	1	NM_020799.4	ENSP00000360994.3	Q96FJ0-1
STAMBPL1	ENST00000371924.5 link	c.428A>G	p.Tyr143Cys	missense_variant	Exon 5 of 10	1		ENSP00000360992.1	Q96FJ0-1
STAMBPL1	ENST00000371927.7 link	c.428A>G	p.Tyr143Cys	missense_variant	Exon 6 of 11	2		ENSP00000360995.3	Q96FJ0-2
STAMBPL1	ENST00000371922.1 link	n.753A>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000430

AC:

AN:

232598

Hom.:

AF XY:

0.00000796

AC XY:

AN XY:

125572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

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:

0.00000278

AC:

AN:

1438272

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428A>G (p.Y143C) alteration is located in exon 6 (coding exon 5) of the STAMBPL1 gene. This alteration results from a A to G substitution at nucleotide position 428, causing the tyrosine (Y) at amino acid position 143 to be replaced by a cysteine (C). 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

0.062

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0074

T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.046

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.12

MutPred

0.26

Gain of methylation at K144 (P = 0.0133);Gain of methylation at K144 (P = 0.0133);Gain of methylation at K144 (P = 0.0133);

MVP

0.35

MPC

0.087

ClinPred

0.35

GERP RS

6.0

Varity_R

0.092

gMVP

0.28

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