rs762585492

Variant names:

• chr10-88913108-A-G
• rs762585492
• NM_020799.4:c.428A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020799.4(STAMBPL1):​c.428A>G​(p.Tyr143Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,438,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09608656).

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.428A>G	p.Tyr143Cys	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.428A>G	p.Tyr143Cys	missense	Exon 6 of 11	ENSP00000360994.3	Q96FJ0-1
	STAMBPL1	ENST00000371924.5	TSL:1	c.428A>G	p.Tyr143Cys	missense	Exon 5 of 10	ENSP00000360992.1	Q96FJ0-1
	STAMBPL1	ENST00000371927.7	TSL:2	c.428A>G	p.Tyr143Cys	missense	Exon 6 of 11	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000430 AC: 1 AN: 232598 AF XY: 0.00000796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1438272 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 713512

African (AFR) AF: 0.00 AC: 0 AN: 32290

American (AMR) AF: 0.00 AC: 0 AN: 40790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24788

East Asian (EAS) AF: 0.0000760 AC: 3 AN: 39466

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101324

Other (OTH) AF: 0.00 AC: 0 AN: 59292

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.046
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.26		Gain of methylation at K144 (P = 0.0133)
MVP		0.35
MPC		0.087
ClinPred		0.35	T
GERP RS		6.0
Varity_R		0.092
gMVP		0.28
Mutation Taster		=70/30	polymorphism

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: rs762585492; hg19: chr10-90672865;