rs34270879

Positions:

• chr10-88913290-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020799.4(STAMBPL1):​c.610G>A​(p.Glu204Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0351 in 1,613,922 control chromosomes in the GnomAD database, including 1,164 homozygotes. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E204D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.029 (91 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1073 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.13

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024805367).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAMBPL1	NM_020799.4	c.610G>A	p.Glu204Lys	missense_variant	6/11	ENST00000371926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.610G>A	p.Glu204Lys	missense_variant	6/11	1	NM_020799.4	P1
STAMBPL1	ENST00000371924.5	c.610G>A	p.Glu204Lys	missense_variant	5/10	1		P1
STAMBPL1	ENST00000371927.7	c.610G>A	p.Glu204Lys	missense_variant	6/11	2
STAMBPL1	ENST00000371922.1	n.935G>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4475 AN: 152208 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00663

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0334

GnomAD3 exomes AF: 0.0305 AC: 7647 AN: 250710 Hom.: 171 AF XY: 0.0315 AC XY: 4274 AN XY: 135506

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.0178

Gnomad ASJ exome AF: 0.0701

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0212

Gnomad FIN exome AF: 0.0395

Gnomad NFE exome AF: 0.0400

Gnomad OTH exome AF: 0.0343

GnomAD4 exome AF: 0.0357 AC: 52210 AN: 1461596 Hom.: 1073 Cov.: 31 AF XY: 0.0358 AC XY: 26027 AN XY: 727106

Gnomad4 AFR exome AF: 0.00658

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0711

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0210

Gnomad4 FIN exome AF: 0.0401

Gnomad4 NFE exome AF: 0.0383

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0294 AC: 4475 AN: 152326 Hom.: 91 Cov.: 32 AF XY: 0.0288 AC XY: 2145 AN XY: 74492

Gnomad4 AFR AF: 0.00664

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0720

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0391 Hom.: 215

Bravo AF: 0.0278

TwinsUK AF: 0.0415 AC: 154

ALSPAC AF: 0.0330 AC: 127

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0429 AC: 369

ExAC AF: 0.0298 AC: 3614

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.0460

EpiControl AF: 0.0466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0035	T;.;T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;.;D
MetaRNN	Benign	0.0025	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.82	T;T;T;T
Polyphen		1.0	D;P;D;.
Vest4		0.36
MPC		0.44
ClinPred		0.028	T
GERP RS		6.0
Varity_R		0.082
gMVP		0.45

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: rs34270879; hg19: chr10-90673047;