NM_020799.4:c.278G>C

Variant names:

• chr10-88908731-G-C
• rs181446155
• NM_020799.4:c.278G>C

Variant summary

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

The NM_020799.4(STAMBPL1):​c.278G>C​(p.Arg93Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,609,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R93Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45
• Publications: 1 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=0.30046487).

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.278G>C	p.Arg93Pro	missense	Exon 4 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.278G>C	p.Arg93Pro	missense	Exon 4 of 11	ENSP00000360994.3	Q96FJ0-1
	STAMBPL1	ENST00000371924.5	TSL:1	c.278G>C	p.Arg93Pro	missense	Exon 3 of 10	ENSP00000360992.1	Q96FJ0-1
	STAMBPL1	ENST00000371927.7	TSL:2	c.278G>C	p.Arg93Pro	missense	Exon 4 of 11	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247060 AF XY: 0.00000748

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: 0.000139

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457452 Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7 AN XY: 724976

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.00 AC: 0 AN: 43732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39394

South Asian (SAS) AF: 0.00 AC: 0 AN: 85452

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110386

Other (OTH) AF: 0.00 AC: 0 AN: 60220

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74186

African (AFR) AF: 0.00 AC: 0 AN: 41348

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.0000948 AC: 1 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		5.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.16
Sift	Benign	0.60	T
Sift4G	Benign	0.81	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.53		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.31
MPC		0.42
ClinPred		0.53	D
GERP RS		5.9
Varity_R		0.30
gMVP		0.53
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs181446155; hg19: chr10-90668488;