rs2232708

chr14-94288467-C-Achr14-94288467-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001100607.3(SERPINA10):c.811G>T(p.Gly271Cys) 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. 12/20 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. G271S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439

Genes affected

SERPINA10 (HGNC:15996): (serpin family A member 10) The protein encoded by this gene belongs to the serpin family. It is predominantly expressed in the liver and secreted in plasma. It inhibits the activity of coagulation factors Xa and XIa in the presence of protein Z, calcium and phospholipid. Mutations in this gene are associated with venous thrombosis. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32563883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA10	NM_001100607.3	c.811G>T	p.Gly271Cys	missense_variant	3/5	ENST00000261994.9
SERPINA10	NM_016186.3	c.811G>T	p.Gly271Cys	missense_variant	3/5
SERPINA10	XM_017021353.2	c.931G>T	p.Gly311Cys	missense_variant	4/6
SERPINA10	XM_005267733.6	c.811G>T	p.Gly271Cys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA10	ENST00000261994.9	c.811G>T	p.Gly271Cys	missense_variant	3/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5	c.931G>T	p.Gly311Cys	missense_variant	3/5	1		P4
SERPINA10	ENST00000393096.5	c.811G>T	p.Gly271Cys	missense_variant	3/5	1		A2
SERPINA10	ENST00000554173.1	c.811G>T	p.Gly271Cys	missense_variant	2/4	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.072	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	-0.34	N;.;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.23
MutPred		0.67		Gain of catalytic residue at M269 (P = 5e-04);.;Gain of catalytic residue at M269 (P = 5e-04);Gain of catalytic residue at M269 (P = 5e-04);
MVP		0.59
MPC		0.21
ClinPred		0.65	D
GERP RS		-2.3
Varity_R		0.41
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2232708; hg19: chr14-94754804; COSMIC: COSV105077605;