10-88913267-G-T

Position:

• chr10-88913267-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020799.4(STAMBPL1):​c.587G>T​(p.Ser196Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S196N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0335128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.587G>T	p.Ser196Ile	missense_variant	6/11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.587G>T	p.Ser196Ile	missense_variant	6/11	1	NM_020799.4	ENSP00000360994.3
STAMBPL1	ENST00000371924.5	c.587G>T	p.Ser196Ile	missense_variant	5/10	1		ENSP00000360992.1
STAMBPL1	ENST00000371927.7	c.587G>T	p.Ser196Ile	missense_variant	6/11	2		ENSP00000360995.3
STAMBPL1	ENST00000371922.1	n.912G>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.00038	T;.;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.73	T;T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.034	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.34	N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.070
MutPred		0.34		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);.;
MVP		0.20
MPC		0.082
ClinPred		0.079	T
GERP RS		3.9
Varity_R		0.046
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs12254856; hg19: chr10-90673024;