chr14-94288445-G-A

Variant names:

• chr14-94288445-G-A
• rs746098136
• NM_001100607.3:c.833C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001100607.3(SERPINA10):​c.833C>T​(p.Thr278Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINA10 NM_001100607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3	c.833C>T	p.Thr278Ile	missense_variant	Exon 3 of 5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3	c.833C>T	p.Thr278Ile	missense_variant	Exon 3 of 5		NP_057270.1
SERPINA10	XM_017021353.2	c.953C>T	p.Thr318Ile	missense_variant	Exon 4 of 6		XP_016876842.1
SERPINA10	XM_005267733.6	c.833C>T	p.Thr278Ile	missense_variant	Exon 3 of 5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA10	ENST00000261994.9	c.833C>T	p.Thr278Ile	missense_variant	Exon 3 of 5	1	NM_001100607.3	ENSP00000261994.4
SERPINA10	ENST00000554723.5	c.953C>T	p.Thr318Ile	missense_variant	Exon 3 of 5	1		ENSP00000450896.1
SERPINA10	ENST00000393096.5	c.833C>T	p.Thr278Ile	missense_variant	Exon 3 of 5	1		ENSP00000376809.1
SERPINA10	ENST00000554173.1	c.833C>T	p.Thr278Ile	missense_variant	Exon 2 of 4	1		ENSP00000450971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	.;T;T;.
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Uncertain	2.6	M;.;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.085	T;T;T;T
Sift4G	Uncertain	0.044	D;D;D;D
Polyphen		0.99	D;.;D;D
Vest4		0.59
MutPred		0.48		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.95
MPC		0.10
ClinPred		0.88	D
GERP RS		4.5
Varity_R		0.44
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746098136; hg19: chr14-94754782;