Variant 14-94288508-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100607.3(SERPINA10):c.770A>G(p.His257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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]

SERPINA10 links:

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ACMG classification

Classification made for transcript

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
SERPINA10	NM_001100607.3 link	c.770A>G	p.His257Arg	missense_variant	3/5	ENST00000261994.9	NP_001094077.1	Q9UK55A0A024R6I6
SERPINA10	NM_016186.3 link	c.770A>G	p.His257Arg	missense_variant	3/5		NP_057270.1	Q9UK55A0A024R6I6
SERPINA10	XM_017021353.2 link	c.890A>G	p.His297Arg	missense_variant	4/6		XP_016876842.1	G3V2W1
SERPINA10	XM_005267733.6 link	c.770A>G	p.His257Arg	missense_variant	3/5		XP_005267790.1	Q9UK55A0A024R6I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINA10	ENST00000261994.9 link	c.770A>G	p.His257Arg	missense_variant	3/5	1	NM_001100607.3	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5 link	c.890A>G	p.His297Arg	missense_variant	3/5	1		ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5 link	c.770A>G	p.His257Arg	missense_variant	3/5	1		ENSP00000376809.1	Q9UK55
SERPINA10	ENST00000554173.1 link	c.770A>G	p.His257Arg	missense_variant	2/4	1		ENSP00000450971.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251432

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.770A>G (p.H257R) alteration is located in exon 3 (coding exon 2) of the SERPINA10 gene. This alteration results from a A to G substitution at nucleotide position 770, causing the histidine (H) at amino acid position 257 to be replaced by an arginine (R). 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

0.084

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.;T;T

Eigen

Benign

0.081

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.54

.;T;T;.

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

1.6

L;.;L;L

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.3

D;D;D;D

REVEL

Uncertain

0.45

Sift

Benign

0.039

D;D;D;D

Sift4G

Benign

0.18

T;T;T;T

Polyphen

1.0

D;.;D;D

Vest4

0.19

MutPred

0.62

Gain of phosphorylation at T255 (P = 0.1156);.;Gain of phosphorylation at T255 (P = 0.1156);Gain of phosphorylation at T255 (P = 0.1156);

MVP

0.82

MPC

0.039

ClinPred

0.37

GERP RS

2.6

Varity_R

0.47

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over