18-63933150-C-T

Position:

• chr18-63933150-C-T

Variant summary

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

The NM_005024.3(SERPINB10):​c.736C>T​(p.Arg246Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,928 control chromosomes in the GnomAD database, including 80,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.41 (15789 hom., cov: 32)
  • Exomes 𝑓: 0.29 (65027 hom.)
• Consequence: SERPINB10 NM_005024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

SERPINB10 (HGNC:8942): (serpin family B member 10) This gene is a member of the serpin peptidase inhibitor, clade B family and is found in a cluster of other similar genes on chromosome 18. The protein encoded by this gene appears to help control the regulation of protease functions during hematopoiesis. Variations in this gene may increase the risk of prostate cancer. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3115061E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.736C>T	p.Arg246Cys	missense_variant	7/8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.736C>T	p.Arg246Cys	missense_variant	8/9		XP_011524329.1
SERPINB10	XM_017025793.2	c.652C>T	p.Arg218Cys	missense_variant	7/8		XP_016881282.1
SERPINB10	XM_011526028.1	c.349C>T	p.Arg117Cys	missense_variant	5/6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.736C>T	p.Arg246Cys	missense_variant	7/8	1	NM_005024.3	ENSP00000238508.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62546 AN: 151860 Hom.: 15746 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.394

GnomAD3 exomes AF: 0.337 AC: 84627 AN: 251276 Hom.: 16379 AF XY: 0.322 AC XY: 43701 AN XY: 135806

Gnomad AFR exome AF: 0.717

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.287 AC: 419302 AN: 1460950 Hom.: 65027 Cov.: 35 AF XY: 0.285 AC XY: 207235 AN XY: 726828

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.412 AC: 62648 AN: 151978 Hom.: 15789 Cov.: 32 AF XY: 0.412 AC XY: 30569 AN XY: 74286

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.399

Alfa AF: 0.287 Hom.: 17748

Bravo AF: 0.436

TwinsUK AF: 0.249 AC: 923

ALSPAC AF: 0.254 AC: 979

ESP6500AA AF: 0.695 AC: 3064

ESP6500EA AF: 0.259 AC: 2224

ExAC AF: 0.336 AC: 40772

Asia WGS AF: 0.410 AC: 1425 AN: 3478

EpiCase AF: 0.270

EpiControl AF: 0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.20	.;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M;M
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.19
Sift	Benign	0.066	T;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.068	B;B
Vest4		0.057
MPC		0.021
ClinPred		0.026	T
GERP RS		0.68
Varity_R		0.14
gMVP		0.49

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: rs963075; hg19: chr18-61600384; COSMIC: COSV53071755;