10-88910970-A-G

Variant names:

• chr10-88910970-A-G
• rs764796438
• NM_020799.4:c.379A>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.379A>G​(p.Lys127Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000009 in 1,444,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000090 (0 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• 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=0.08645624).

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.379A>G	p.Lys127Glu	missense	Exon 5 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.379A>G	p.Lys127Glu	missense	Exon 5 of 11	ENSP00000360994.3	Q96FJ0-1
	STAMBPL1	ENST00000371924.5	TSL:1	c.379A>G	p.Lys127Glu	missense	Exon 4 of 10	ENSP00000360992.1	Q96FJ0-1
	STAMBPL1	ENST00000371927.7	TSL:2	c.379A>G	p.Lys127Glu	missense	Exon 5 of 11	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000900 AC: 13 AN: 1444798 Hom.: 0 Cov.: 29 AF XY: 0.00000697 AC XY: 5 AN XY: 717846

African (AFR) AF: 0.00 AC: 0 AN: 32692

American (AMR) AF: 0.00 AC: 0 AN: 41356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39102

South Asian (SAS) AF: 0.00 AC: 0 AN: 80830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1106342

Other (OTH) AF: 0.00 AC: 0 AN: 59774

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.50	N
PhyloP100		4.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.052
Sift	Benign	0.47	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.36		Loss of ubiquitination at K127 (P = 0.0134)
MVP		0.41
MPC		0.097
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.22
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs764796438; hg19: chr10-90670727;