10-88916773-A-C

Position:

• chr10-88916773-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020799.4(STAMBPL1):​c.997A>C​(p.Asn333His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10977414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.997A>C	p.Asn333His	missense_variant	8/11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.997A>C	p.Asn333His	missense_variant	8/11	1	NM_020799.4	ENSP00000360994	P1
STAMBPL1	ENST00000371924.5	c.997A>C	p.Asn333His	missense_variant	7/10	1		ENSP00000360992	P1
STAMBPL1	ENST00000371927.7	c.997A>C	p.Asn333His	missense_variant	8/11	2		ENSP00000360995
STAMBPL1	ENST00000371922.1	n.1322A>C		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

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

Feb 28, 2023

The c.997A>C (p.N333H) alteration is located in exon 8 (coding exon 7) of the STAMBPL1 gene. This alteration results from a A to C substitution at nucleotide position 997, causing the asparagine (N) at amino acid position 333 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	0.055
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.1
DANN	Benign	0.93
DEOGEN2	Benign	0.0098	T;.;T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.78	T;T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.88	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.11	B;B;B;.
Vest4		0.32
MutPred		0.39		Loss of catalytic residue at N333 (P = 0.2278);Loss of catalytic residue at N333 (P = 0.2278);Loss of catalytic residue at N333 (P = 0.2278);.;
MVP		0.44
MPC		0.10
ClinPred		0.030	T
GERP RS		-3.1
Varity_R		0.12
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-90676530;