10-88910982-G-T

Variant names:

• chr10-88910982-G-T
• rs148947892
• NM_020799.4:c.391G>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.391G>T​(p.Val131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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 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=0.019899368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.391G>T	p.Val131Leu	missense_variant	Exon 5 of 11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.391G>T	p.Val131Leu	missense_variant	Exon 5 of 11	1	NM_020799.4	ENSP00000360994.3
STAMBPL1	ENST00000371924.5	c.391G>T	p.Val131Leu	missense_variant	Exon 4 of 10	1		ENSP00000360992.1
STAMBPL1	ENST00000371927.7	c.391G>T	p.Val131Leu	missense_variant	Exon 5 of 11	2		ENSP00000360995.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440260 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 715436

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.84
DEOGEN2	Benign	0.22	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.26	T;T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.020	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.13
MutPred		0.25		Gain of catalytic residue at V131 (P = 0.0466);Gain of catalytic residue at V131 (P = 0.0466);Gain of catalytic residue at V131 (P = 0.0466);
MVP		0.072
MPC		0.069
ClinPred		0.049	T
GERP RS		-3.3
Varity_R		0.035
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs148947892; hg19: chr10-90670739;