10-88913182-C-G

Variant names:

• chr10-88913182-C-G
• rs1297419511
• NM_020799.4:c.502C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020799.4(STAMBPL1):​c.502C>G​(p.Arg168Gly) 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. 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. R168H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30325565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020799.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBPL1	NM_020799.4	MANE Select	c.502C>G	p.Arg168Gly	missense	Exon 6 of 11	NP_065850.1	Q96FJ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBPL1	ENST00000371926.8	TSL:1 MANE Select	c.502C>G	p.Arg168Gly	missense	Exon 6 of 11	ENSP00000360994.3	Q96FJ0-1
	STAMBPL1	ENST00000371924.5	TSL:1	c.502C>G	p.Arg168Gly	missense	Exon 5 of 10	ENSP00000360992.1	Q96FJ0-1
	STAMBPL1	ENST00000371927.7	TSL:2	c.502C>G	p.Arg168Gly	missense	Exon 6 of 11	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250570 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.93
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.012	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.25		Loss of MoRF binding (P = 0.0421)
MVP		0.36
MPC		0.47
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.50
gMVP		0.53
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs1297419511; hg19: chr10-90672939; COSMIC: COSV100904988;