18-63918026-T-C

Variant names:

• chr18-63918026-T-C
• rs724558
• NM_005024.3:c.296T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005024.3(SERPINB10):​c.296T>C​(p.Ile99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,611,484 control chromosomes in the GnomAD database, including 33,831 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.

• Frequency:
  • Genomes: 𝑓 0.24 (4503 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29328 hom.)
• Consequence: SERPINB10 NM_005024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016202629).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.296T>C	p.Ile99Thr	missense_variant	Exon 4 of 8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.296T>C	p.Ile99Thr	missense_variant	Exon 5 of 9		XP_011524329.1
SERPINB10	XM_017025793.2	c.296T>C	p.Ile99Thr	missense_variant	Exon 4 of 8		XP_016881282.1
SERPINB10	XM_011526028.1	c.-241T>C		5_prime_UTR_variant	Exon 1 of 6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.296T>C	p.Ile99Thr	missense_variant	Exon 4 of 8	1	NM_005024.3	ENSP00000238508.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35833 AN: 151808 Hom.: 4494 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.223 AC: 55782 AN: 250570 AF XY: 0.215

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.219

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.196 AC: 286712 AN: 1459558 Hom.: 29328 Cov.: 31 AF XY: 0.196 AC XY: 142047 AN XY: 726150

African (AFR) AF: 0.319 AC: 10656 AN: 33368

American (AMR) AF: 0.348 AC: 15498 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3884 AN: 26070

East Asian (EAS) AF: 0.171 AC: 6761 AN: 39622

South Asian (SAS) AF: 0.190 AC: 16355 AN: 86176

European-Finnish (FIN) AF: 0.196 AC: 10426 AN: 53296

Middle Eastern (MID) AF: 0.224 AC: 1287 AN: 5750

European-Non Finnish (NFE) AF: 0.189 AC: 209473 AN: 1110454

Other (OTH) AF: 0.205 AC: 12372 AN: 60272

GnomAD4 genome AF: 0.236 AC: 35879 AN: 151926 Hom.: 4503 Cov.: 32 AF XY: 0.238 AC XY: 17708 AN XY: 74258

African (AFR) AF: 0.310 AC: 12835 AN: 41470

American (AMR) AF: 0.315 AC: 4792 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1124 AN: 5144

South Asian (SAS) AF: 0.202 AC: 973 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10566

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12816 AN: 67914

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.200 Hom.: 8926

Bravo AF: 0.250

TwinsUK AF: 0.169 AC: 627

ALSPAC AF: 0.183 AC: 706

ESP6500AA AF: 0.313 AC: 1379

ESP6500EA AF: 0.187 AC: 1609

ExAC AF: 0.216 AC: 26265

Asia WGS AF: 0.218 AC: 757 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.59	.;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		3.5
PROVEAN	Uncertain	-3.9	D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0090	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.13
MPC		0.13
ClinPred		0.013	T
GERP RS		5.8
Varity_R		0.45
gMVP		0.34
Mutation Taster		=93/7	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: rs724558; hg19: chr18-61585260; COSMIC: COSV53072338; COSMIC: COSV53072338;