chr10-88921299-C-G

Position:

• chr10-88921299-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_020799.4(STAMBPL1):​c.1058C>G​(p.Thr353Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a mutagenesis_site 19-fold decrease in activity, no change in substrate affinity. (size 0) in uniprot entity STALP_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.1058C>G	p.Thr353Ser	missense_variant	9/11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.1058C>G	p.Thr353Ser	missense_variant	9/11	1	NM_020799.4	ENSP00000360994	P1
STAMBPL1	ENST00000371924.5	c.1058C>G	p.Thr353Ser	missense_variant	8/10	1		ENSP00000360992	P1
STAMBPL1	ENST00000371927.7	c.1058C>G	p.Thr353Ser	missense_variant	9/11	2		ENSP00000360995
STAMBPL1	ENST00000371922.1	n.1383C>G		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.1058C>G (p.T353S) alteration is located in exon 9 (coding exon 8) of the STAMBPL1 gene. This alteration results from a C to G substitution at nucleotide position 1058, causing the threonine (T) at amino acid position 353 to be replaced by a serine (S). 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	0.22
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.59	P;P;P;.
Vest4		0.90
MutPred		0.57		Gain of disorder (P = 0.0438);Gain of disorder (P = 0.0438);Gain of disorder (P = 0.0438);.;
MVP		0.76
MPC		0.15
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.86
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90681056;