chr18-63935139-G-T

Position:

• chr18-63935139-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005024.3(SERPINB10):​c.1091G>T​(p.Arg364Ile) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB10 NM_005024.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.81

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07391068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.1091G>T	p.Arg364Ile	missense_variant	8/8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.1091G>T	p.Arg364Ile	missense_variant	9/9		XP_011524329.1
SERPINB10	XM_017025793.2	c.1007G>T	p.Arg336Ile	missense_variant	8/8		XP_016881282.1
SERPINB10	XM_011526028.1	c.704G>T	p.Arg235Ile	missense_variant	6/6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.1091G>T	p.Arg364Ile	missense_variant	8/8	1	NM_005024.3	ENSP00000238508	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.1091G>T (p.R364I) alteration is located in exon 7 (coding exon 7) of the SERPINB10 gene. This alteration results from a G to T substitution at nucleotide position 1091, causing the arginine (R) at amino acid position 364 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.024
DANN	Benign	0.85
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.45	.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.29
Sift	Benign	0.43	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.11	B;B
Vest4		0.081
MutPred		0.49		Loss of catalytic residue at R364 (P = 0.0013);Loss of catalytic residue at R364 (P = 0.0013);
MVP		0.40
MPC		0.027
ClinPred		0.23	T
GERP RS		-9.0
Varity_R		0.040
gMVP		0.18

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: rs1289853589; hg19: chr18-61602373;