Variant chr14-94614436-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001085.5(SERPINA3):c.-6T>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SERPINA3
NM_001085.5 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.00002784

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.511

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 14-94614436-T-C is Benign according to our data. Variant chr14-94614436-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039814.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SERPINA3	NM_001085.5 linkuse as main transcript	c.-6T>C	splice_region_variant, 5_prime_UTR_variant	2/5	ENST00000393078.5
SERPINA3	NM_001384672.1 linkuse as main transcript	c.-6T>C	splice_region_variant, 5_prime_UTR_variant	2/5
SERPINA3	NM_001384673.1 linkuse as main transcript	c.-6T>C	splice_region_variant, 5_prime_UTR_variant	3/6
SERPINA3	NM_001384674.1 linkuse as main transcript	c.-6T>C	splice_region_variant, 5_prime_UTR_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA3	ENST00000393078.5 linkuse as main transcript	c.-6T>C		splice_region_variant, 5_prime_UTR_variant	2/5	1	NM_001085.5	P1	P01011-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000284

AC:

AN:

249840

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.00415

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000120

AC:

176

AN:

1461032

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00457

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.00130

AC:

197

AN:

152090

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00458

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000331

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SERPINA3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as likely 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

-0.86

CADD

Benign

0.39

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

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