Variant 14-94614744-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001085.5(SERPINA3):c.303A>G(p.Lys101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,614,086 control chromosomes in the GnomAD database, including 8,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 536 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8109 hom. )

Consequence

SERPINA3
NM_001085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.311

Variant links:

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

SERPINA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-94614744-A-G is Benign according to our data. Variant chr14-94614744-A-G is described in ClinVar as [Benign]. Clinvar id is 403428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.311 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA3	NM_001085.5 linkuse as main transcript	c.303A>G	p.Lys101=	synonymous_variant	2/5	ENST00000393078.5
SERPINA3	NM_001384672.1 linkuse as main transcript	c.303A>G	p.Lys101=	synonymous_variant	2/5
SERPINA3	NM_001384673.1 linkuse as main transcript	c.303A>G	p.Lys101=	synonymous_variant	3/6
SERPINA3	NM_001384674.1 linkuse as main transcript	c.303A>G	p.Lys101=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA3	ENST00000393078.5 linkuse as main transcript	c.303A>G	p.Lys101=	synonymous_variant	2/5	1	NM_001085.5	P1	P01011-1

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

11111

AN:

152102

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.0751

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0891

GnomAD3 exomes

AF:

0.0809

AC:

20330

AN:

251304

Hom.:

1043

AF XY:

0.0836

AC XY:

11352

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.0592

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.0439

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.0959

GnomAD4 exome

AF:

0.101

AC:

147080

AN:

1461866

Hom.:

8109

Cov.:

AF XY:

0.100

AC XY:

73043

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.0607

Gnomad4 ASJ exome

AF:

0.0993

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.0780

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0729

AC:

11100

AN:

152220

Hom.:

536

Cov.:

AF XY:

0.0698

AC XY:

5195

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.0750

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.0713

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0891

Alfa

AF:

0.107

Hom.:

1639

Bravo

AF:

0.0737

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

SERPINA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

DANN

Benign

0.46

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