Variant chr14-94614477-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001085.5(SERPINA3):c.36C>T(p.Leu12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,614,102 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 31 hom. )

Consequence

SERPINA3
NM_001085.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.682

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 14-94614477-C-T is Benign according to our data. Variant chr14-94614477-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 789642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.682 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA3	NM_001085.5 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	2/5	ENST00000393078.5
SERPINA3	NM_001384672.1 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	2/5
SERPINA3	NM_001384673.1 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	3/6
SERPINA3	NM_001384674.1 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA3	ENST00000393078.5 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	2/5	1	NM_001085.5	P1	P01011-1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

674

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00808

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00657

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00502

AC:

1262

AN:

251270

Hom.:

AF XY:

0.00517

AC XY:

702

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00418

Gnomad FIN exome

AF:

0.00763

Gnomad NFE exome

AF:

0.00677

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00620

AC:

9067

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

4453

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00464

Gnomad4 FIN exome

AF:

0.00813

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00596

GnomAD4 genome

AF:

0.00443

AC:

674

AN:

152252

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

326

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00808

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.00657

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00686

Hom.:

Bravo

AF:

0.00438

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00486

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	SERPINA3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.75

DANN

Benign

0.66

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

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