NM_020799.4:c.610G>A

Variant names:

• chr10-88913290-G-A
• rs34270879
• NM_020799.4:c.610G>A

Variant summary

Our verdict is Benign. The variant received -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 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
• Publications: 14 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBPL1	NM_020799.4	MANE Select	c.610G>A	p.Glu204Lys	missense	Exon 6 of 11	NP_065850.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBPL1	ENST00000371926.8	TSL:1 MANE Select	c.610G>A	p.Glu204Lys	missense	Exon 6 of 11	ENSP00000360994.3
	STAMBPL1	ENST00000371924.5	TSL:1	c.610G>A	p.Glu204Lys	missense	Exon 5 of 10	ENSP00000360992.1
	STAMBPL1	ENST00000371927.7	TSL:2	c.610G>A	p.Glu204Lys	missense	Exon 6 of 11	ENSP00000360995.3

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

GnomAD2 exomes AF: 0.0305 AC: 7647 AN: 250710 AF XY: 0.0315

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 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

African (AFR) AF: 0.00658 AC: 220 AN: 33452

American (AMR) AF: 0.0187 AC: 836 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 1856 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0210 AC: 1810 AN: 86250

European-Finnish (FIN) AF: 0.0401 AC: 2144 AN: 53418

Middle Eastern (MID) AF: 0.0774 AC: 446 AN: 5764

European-Non Finnish (NFE) AF: 0.0383 AC: 42624 AN: 1111844

Other (OTH) AF: 0.0376 AC: 2272 AN: 60372

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

African (AFR) AF: 0.00664 AC: 276 AN: 41584

American (AMR) AF: 0.0309 AC: 473 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4832

European-Finnish (FIN) AF: 0.0390 AC: 414 AN: 10616

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0407 AC: 2770 AN: 68020

Other (OTH) AF: 0.0331 AC: 70 AN: 2116

Alfa AF: 0.0367 Hom.: 425

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 v4.9

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
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.20	T
Sift4G	Benign	0.82	T
Polyphen		1.0	D
Vest4		0.36
MPC		0.44
ClinPred		0.028	T
GERP RS		6.0
Varity_R		0.082
gMVP		0.45
Mutation Taster		=90/10	polymorphism (auto)

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: rs34270879; hg19: chr10-90673047; COSMIC: COSV107456929;