rs724558

Positions:

• chr18-63918026-T-A
• chr18-63918026-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005024.3(SERPINB10):​c.296T>A​(p.Ile99Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. I99T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINB10 NM_005024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.296T>A	p.Ile99Asn	missense_variant	4/8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.296T>A	p.Ile99Asn	missense_variant	5/9		XP_011524329.1
SERPINB10	XM_017025793.2	c.296T>A	p.Ile99Asn	missense_variant	4/8		XP_016881282.1
SERPINB10	XM_011526028.1	c.-241T>A		5_prime_UTR_variant	1/6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.296T>A	p.Ile99Asn	missense_variant	4/8	1	NM_005024.3	ENSP00000238508	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726420

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	0.010	P
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.78
MutPred		0.49		Gain of disorder (P = 0.0216);Gain of disorder (P = 0.0216);
MVP		0.94
MPC		0.16
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.86
gMVP		0.61

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: rs724558; hg19: chr18-61585260;