Genetic Variant SERPINA10:p.Arg88* (chr14-94290332-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001100607.3(SERPINA10):c.262C>T(p.Arg88*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,614,230 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 78 hom. )

Consequence

SERPINA10
NM_001100607.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.99

Publications

37 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001100607.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-94290332-G-A is Benign according to our data. Variant chr14-94290332-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 979156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA10	NM_001100607.3	MANE Select	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	NP_001094077.1	Q9UK55
	SERPINA10	NM_016186.3		c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	NP_057270.1	Q9UK55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA10	ENST00000261994.9	TSL:1 MANE Select	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5	TSL:1	c.382C>T	p.Arg128*	stop_gained	Exon 2 of 5	ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5	TSL:1	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	ENSP00000376809.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.00630

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00718

AC:

1802

AN:

251086

AF XY:

0.00797

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00657

AC:

9604

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00702

AC XY:

5105

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

33480

American (AMR)

AF:

0.00686

AC:

307

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

512

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0160

AC:

1382

AN:

86256

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0695

AC:

401

AN:

5768

European-Non Finnish (NFE)

AF:

0.00565

AC:

6281

AN:

1112006

Other (OTH)

AF:

0.00901

AC:

544

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

678

1356

2033

2711

3389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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

AF:

0.00530

AC:

808

AN:

152346

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

413

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41590

American (AMR)

AF:

0.00764

AC:

117

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0139

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00631

AC:

429

AN:

68038

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00715

Hom.:

Bravo

AF:

0.00521

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.00942

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

LAMB2-related infantile-onset nephrotic syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.77

PhyloP100

2.0

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=162/38

disease causing (fs/PTC)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over