rs12254856

chr10-88913267-G-Achr10-88913267-G-T

Variant summary

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

The NM_020799.4(STAMBPL1):c.587G>A(p.Ser196Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,812 control chromosomes in the GnomAD database, including 16,044 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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.

• Frequency:
  • Genomes: 𝑓 0.13 (1420 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14624 hom.)
• Consequence: STAMBPL1 NM_020799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=0.0011698604).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAMBPL1	NM_020799.4	c.587G>A	p.Ser196Asn	missense_variant	6/11	ENST00000371926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.587G>A	p.Ser196Asn	missense_variant	6/11	1	NM_020799.4	P1
STAMBPL1	ENST00000371924.5	c.587G>A	p.Ser196Asn	missense_variant	5/10	1		P1
STAMBPL1	ENST00000371927.7	c.587G>A	p.Ser196Asn	missense_variant	6/11	2
STAMBPL1	ENST00000371922.1	n.912G>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19670 AN: 152114 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0840

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.108 AC: 26962 AN: 250718 Hom.: 1702 AF XY: 0.107 AC XY: 14494 AN XY: 135472

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0824

Gnomad ASJ exome AF: 0.0875

Gnomad EAS exome AF: 0.00142

Gnomad SAS exome AF: 0.0714

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.137 AC: 199841 AN: 1461580 Hom.: 14624 Cov.: 31 AF XY: 0.135 AC XY: 97897 AN XY: 727094

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0859

Gnomad4 ASJ exome AF: 0.0875

Gnomad4 EAS exome AF: 0.000605

Gnomad4 SAS exome AF: 0.0745

Gnomad4 FIN exome AF: 0.0785

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.129 AC: 19688 AN: 152232 Hom.: 1420 Cov.: 32 AF XY: 0.123 AC XY: 9183 AN XY: 74432

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0840

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.102

Alfa AF: 0.138 Hom.: 3834

Bravo AF: 0.133

ESP6500AA AF: 0.160 AC: 705

ESP6500EA AF: 0.143 AC: 1228

ExAC AF: 0.111 AC: 13479

Asia WGS AF: 0.0410 AC: 144 AN: 3478

EpiCase AF: 0.146

EpiControl AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	16
Dann	Benign	0.93
DEOGEN2	Benign	0.0045	T;.;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.59	T;T;.;T
MetaRNN	Benign	0.0012	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.71	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.49	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.029
MPC		0.066
ClinPred		0.0017	T
GERP RS		3.9
Varity_R		0.042
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12254856; hg19: chr10-90673024; COSMIC: COSV64222745;