rs373894376

Variant names:

• chr10-88914588-A-C
• rs373894376
• NM_020799.4:c.833A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-88914588-A-C
• chr10-88914588-A-G

Variant summary

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

The NM_020799.4(STAMBPL1):​c.833A>C​(p.Lys278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

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 rank	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.833A>C	p.Lys278Thr	missense_variant	Exon 7 of 11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.833A>C	p.Lys278Thr	missense_variant	Exon 7 of 11	1	NM_020799.4	ENSP00000360994.3
STAMBPL1	ENST00000371924.5	c.833A>C	p.Lys278Thr	missense_variant	Exon 6 of 10	1		ENSP00000360992.1
STAMBPL1	ENST00000371927.7	c.833A>C	p.Lys278Thr	missense_variant	Exon 7 of 11	2		ENSP00000360995.3
STAMBPL1	ENST00000371922.1	n.1158A>C		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T;.;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;D;.;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L;L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D;T;D;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.090	B;B;B;.
Vest4		0.54
MutPred		0.55		Loss of ubiquitination at K278 (P = 0.0192);Loss of ubiquitination at K278 (P = 0.0192);Loss of ubiquitination at K278 (P = 0.0192);.;
MVP		0.45
MPC		0.16
ClinPred		0.60	D
GERP RS		-3.7
Varity_R		0.25
gMVP		0.63

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

Other links and lift over

dbSNP: rs373894376; hg19: chr10-90674345;