chr18-63934988-G-A

Position:

• chr18-63934988-G-A

Variant summary

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

The NM_005024.3(SERPINB10):​c.940G>A​(p.Ala314Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.88

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3	c.940G>A	p.Ala314Thr	missense_variant	8/8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2	c.940G>A	p.Ala314Thr	missense_variant	9/9		XP_011524329.1
SERPINB10	XM_017025793.2	c.856G>A	p.Ala286Thr	missense_variant	8/8		XP_016881282.1
SERPINB10	XM_011526028.1	c.553G>A	p.Ala185Thr	missense_variant	6/6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8	c.940G>A	p.Ala314Thr	missense_variant	8/8	1	NM_005024.3	ENSP00000238508	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 09, 2024

The c.940G>A (p.A314T) alteration is located in exon 7 (coding exon 7) of the SERPINB10 gene. This alteration results from a G to A substitution at nucleotide position 940, causing the alanine (A) at amino acid position 314 to be replaced by a threonine (T). 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	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.7	H;H
MutationTaster	Benign	0.85	D
PROVEAN	Uncertain	-3.4	D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.020	D;D
Polyphen		0.98	D;D
Vest4		0.34
MutPred		0.52		Gain of phosphorylation at A314 (P = 0.0337);Gain of phosphorylation at A314 (P = 0.0337);
MVP		0.97
MPC		0.14
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.71
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61602222;