rs963075

chr18-63933150-C-Achr18-63933150-C-Gchr18-63933150-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005024.3(SERPINB10):c.736C>A(p.Arg246Ser) 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 benign outcome for this variant. 15/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R246C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059794188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB10	NM_005024.3	c.736C>A	p.Arg246Ser	missense_variant	7/8	ENST00000238508.8
SERPINB10	XM_011526027.2	c.736C>A	p.Arg246Ser	missense_variant	8/9
SERPINB10	XM_017025793.2	c.652C>A	p.Arg218Ser	missense_variant	7/8
SERPINB10	XM_011526028.1	c.349C>A	p.Arg117Ser	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB10	ENST00000238508.8	c.736C>A	p.Arg246Ser	missense_variant	7/8	1	NM_005024.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	9.0
Dann	Benign	0.83
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.051	N
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.71	N;N
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.091
Sift	Benign	0.40	T;.
Sift4G	Uncertain	0.040	D;D
Polyphen		0.058	B;B
Vest4		0.13
MutPred		0.40		Gain of ubiquitination at K244 (P = 0.0872);Gain of ubiquitination at K244 (P = 0.0872);
MVP		0.64
MPC		0.020
ClinPred		0.051	T
GERP RS		0.68
Varity_R		0.17
gMVP		0.45

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;