Variant 14-94290320-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100607.3(SERPINA10):c.274A>T(p.Met92Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049610734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA10	NM_001100607.3 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	2/5	ENST00000261994.9
SERPINA10	NM_016186.3 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	2/5
SERPINA10	XM_017021353.2 linkuse as main transcript	c.394A>T	p.Met132Leu	missense_variant	3/6
SERPINA10	XM_005267733.6 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.394A>T	p.Met132Leu	missense_variant	2/5	1		P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	2/5	1		A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	1/4	1		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Oct 12, 2022

The c.274A>T (p.M92L) alteration is located in exon 2 (coding exon 1) of the SERPINA10 gene. This alteration results from a A to T substitution at nucleotide position 274, causing the methionine (M) at amino acid position 92 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

1.9

DANN

Benign

0.59

DEOGEN2

Benign

0.13

T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.48

.;T;T;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.050

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.095

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.097

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0020

B;.;B;B

Vest4

0.22

MutPred

0.36

Loss of MoRF binding (P = 0.0769);.;Loss of MoRF binding (P = 0.0769);Loss of MoRF binding (P = 0.0769);

MVP

0.13

MPC

0.025

ClinPred

0.031

GERP RS

-3.0

Varity_R

0.38

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over