chr14-94614436-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001085.5(SERPINA3):c.-6T>C variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SERPINA3
NM_001085.5 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.00002784

Clinical Significance

Likely benign no assertion criteria provided 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:

ENSG00000273259 (HGNC:):

ENSG00000273259 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINA3	NM_001085.5 link	c.-6T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0
SERPINA3	NM_001085.5 link	c.-6T>C	splice_region_variant	Exon 2 of 5	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0
SERPINA3	NM_001085.5 link	c.-6T>C	5_prime_UTR_variant	Exon 2 of 5	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA3	ENST00000393078 link	c.-6T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	1	NM_001085.5	ENSP00000376793.3	P01011-1
SERPINA3	ENST00000393078.5 link	c.-6T>C	splice_region_variant	Exon 2 of 5	1	NM_001085.5	ENSP00000376793.3	P01011-1
SERPINA3	ENST00000393078 link	c.-6T>C	5_prime_UTR_variant	Exon 2 of 5	1	NM_001085.5	ENSP00000376793.3	P01011-1
ENSG00000273259	ENST00000553947.1 link	n.*821T>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000452367.2	G3V5I3
ENSG00000273259	ENST00000553947.1 link	n.*821T>C	3_prime_UTR_variant	Exon 5 of 8	2		ENSP00000452367.2	G3V5I3

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

GnomAD2 exomes

AF:

0.000284

AC:

AN:

249840

AF XY:

0.000185

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 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

AC:

153

AN:

33480

Gnomad4 AMR exome

AF:

0.0000671

AC:

AN:

44722

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000232

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52618

Gnomad4 NFE exome

AF:

0.00000450

AC:

AN:

1111974

Gnomad4 Remaining exome

AF:

0.000166

AC:

AN:

60380

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

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

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

AC:

0.00457964

AN:

0.00457964

Gnomad4 AMR

AF:

0.000196

AC:

0.000196232

AN:

0.000196232

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00190

AC:

0.00190114

AN:

0.00190114

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.000331

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SERPINA3-related disorder

Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Mutation Taster

=300/0

polymorphism

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