14-94290332-G-C

Position:

• chr14-94290332-G-C

Variant summary

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

The NM_001100607.3(SERPINA10):​c.262C>G​(p.Arg88Gly) 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. R88Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA10	NM_001100607.3	c.262C>G	p.Arg88Gly	missense_variant	2/5	ENST00000261994.9
SERPINA10	NM_016186.3	c.262C>G	p.Arg88Gly	missense_variant	2/5
SERPINA10	XM_017021353.2	c.382C>G	p.Arg128Gly	missense_variant	3/6
SERPINA10	XM_005267733.6	c.262C>G	p.Arg88Gly	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA10	ENST00000261994.9	c.262C>G	p.Arg88Gly	missense_variant	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5	c.382C>G	p.Arg128Gly	missense_variant	2/5	1		P4
SERPINA10	ENST00000393096.5	c.262C>G	p.Arg88Gly	missense_variant	2/5	1		A2
SERPINA10	ENST00000554173.1	c.262C>G	p.Arg88Gly	missense_variant	1/4	1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.;T;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	.;T;T;.
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.7	H;.;H;H
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.65
MutPred		0.73		Loss of MoRF binding (P = 0.018);.;Loss of MoRF binding (P = 0.018);Loss of MoRF binding (P = 0.018);
MVP		0.72
MPC		0.22
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.89
gMVP		0.54

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: rs2232698; hg19: chr14-94756669;