Variant chr14-94614699-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001085.5(SERPINA3):c.258C>T(p.Phe86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,614,180 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

SERPINA3
NM_001085.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.34

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 14-94614699-C-T is Benign according to our data. Variant chr14-94614699-C-T is described in ClinVar as [Benign]. Clinvar id is 789820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.34 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA3	NM_001085.5 linkuse as main transcript	c.258C>T	p.Phe86=	synonymous_variant	2/5	ENST00000393078.5
SERPINA3	NM_001384672.1 linkuse as main transcript	c.258C>T	p.Phe86=	synonymous_variant	2/5
SERPINA3	NM_001384673.1 linkuse as main transcript	c.258C>T	p.Phe86=	synonymous_variant	3/6
SERPINA3	NM_001384674.1 linkuse as main transcript	c.258C>T	p.Phe86=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA3	ENST00000393078.5 linkuse as main transcript	c.258C>T	p.Phe86=	synonymous_variant	2/5	1	NM_001085.5	P1	P01011-1

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

690

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00130

AC:

328

AN:

251352

Hom.:

AF XY:

0.000972

AC XY:

132

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000583

AC:

853

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

400

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00454

AC:

692

AN:

152286

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00476

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.6

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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