10-88913267-G-A

Variant names:

• chr10-88913267-G-A
• rs12254856
• NM_020799.4:c.587G>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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 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=0.0011698604).
• 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 rank	MANE	Protein	UniProt
STAMBPL1	NM_020799.4	c.587G>A	p.Ser196Asn	missense_variant	Exon 6 of 11	ENST00000371926.8	NP_065850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAMBPL1	ENST00000371926.8	c.587G>A	p.Ser196Asn	missense_variant	Exon 6 of 11	1	NM_020799.4	ENSP00000360994.3
STAMBPL1	ENST00000371924.5	c.587G>A	p.Ser196Asn	missense_variant	Exon 5 of 10	1		ENSP00000360992.1
STAMBPL1	ENST00000371927.7	c.587G>A	p.Ser196Asn	missense_variant	Exon 6 of 11	2		ENSP00000360995.3
STAMBPL1	ENST00000371922.1	n.912G>A		non_coding_transcript_exon_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.108 AC: 26962 AN: 250718 AF XY: 0.107

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 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

African (AFR) AF: 0.155 AC: 5176 AN: 33448

American (AMR) AF: 0.0859 AC: 3836 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0875 AC: 2286 AN: 26124

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39688

South Asian (SAS) AF: 0.0745 AC: 6424 AN: 86250

European-Finnish (FIN) AF: 0.0785 AC: 4195 AN: 53416

Middle Eastern (MID) AF: 0.0932 AC: 537 AN: 5762

European-Non Finnish (NFE) AF: 0.152 AC: 169532 AN: 1111840

Other (OTH) AF: 0.130 AC: 7831 AN: 60380

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

African (AFR) AF: 0.154 AC: 6392 AN: 41530

American (AMR) AF: 0.111 AC: 1701 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0840 AC: 291 AN: 3466

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5190

South Asian (SAS) AF: 0.0714 AC: 345 AN: 4830

European-Finnish (FIN) AF: 0.0738 AC: 783 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9854 AN: 68002

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.138 Hom.: 5338

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;.
PhyloP100		1.3
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12254856; hg19: chr10-90673024; COSMIC: COSV64222745;