Genetic Variant SERPINA10:p.Lys46Thr (chr14-94290457-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100607.3(SERPINA10):c.137A>C(p.Lys46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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: 0.0000034 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.48

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06085977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 2 of 5	ENST00000261994.9	NP_001094077.1	Q9UK55A0A024R6I6
SERPINA10	NM_016186.3 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 2 of 5		NP_057270.1	Q9UK55A0A024R6I6
SERPINA10	XM_017021353.2 link	c.257A>C	p.Lys86Thr	missense_variant	Exon 3 of 6		XP_016876842.1	G3V2W1
SERPINA10	XM_005267733.6 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 2 of 5		XP_005267790.1	Q9UK55A0A024R6I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA10	ENST00000261994.9 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 2 of 5	1	NM_001100607.3	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5 link	c.257A>C	p.Lys86Thr	missense_variant	Exon 2 of 5	1		ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 2 of 5	1		ENSP00000376809.1	Q9UK55
SERPINA10	ENST00000554173.1 link	c.137A>C	p.Lys46Thr	missense_variant	Exon 1 of 4	1		ENSP00000450971.1	Q9UK55

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460956

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111468

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.010

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.042

T;.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.35

.;T;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

N;.;N;N

PhyloP100

-4.5

PrimateAI

Benign

0.20

PROVEAN

Benign

0.050

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.58

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.17

MutPred

0.24

Loss of ubiquitination at K46 (P = 0.0019);.;Loss of ubiquitination at K46 (P = 0.0019);Loss of ubiquitination at K46 (P = 0.0019);

MVP

0.15

MPC

0.028

ClinPred

0.036

GERP RS

-0.49

PromoterAI

-0.0015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.35

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over