10-88905480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020799.4(STAMBPL1):c.68C>T(p.Ser23Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAMBPL1	NM_020799.4	c.68C>T	p.Ser23Phe	missense_variant	3/11	ENST00000371926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.68C>T	p.Ser23Phe	missense_variant	3/11	1	NM_020799.4	P1
STAMBPL1	ENST00000371924.5	c.68C>T	p.Ser23Phe	missense_variant	2/10	1		P1
STAMBPL1	ENST00000371927.7	c.68C>T	p.Ser23Phe	missense_variant	3/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727210

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

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

Oct 06, 2021

The c.68C>T (p.S23F) alteration is located in exon 3 (coding exon 2) of the STAMBPL1 gene. This alteration results from a C to T substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a phenylalanine (F). 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T
Eigen	Benign	0.0073
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.29		Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);
MVP		0.38
MPC		0.40
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.35
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90665237;