Variant chr14-94614569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085.5(SERPINA3):c.128C>T(p.Thr43Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SERPINA3
NM_001085.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.33

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16257927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA3	NM_001085.5 link	c.128C>T	p.Thr43Ile	missense_variant	2/5	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0
SERPINA3	NM_001384672.1 link	c.128C>T	p.Thr43Ile	missense_variant	2/5		NP_001371601.1
SERPINA3	NM_001384673.1 link	c.128C>T	p.Thr43Ile	missense_variant	3/6		NP_001371602.1
SERPINA3	NM_001384674.1 link	c.128C>T	p.Thr43Ile	missense_variant	3/6		NP_001371603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINA3	ENST00000393078.5 link	c.128C>T	p.Thr43Ile	missense_variant	2/5	1	NM_001085.5	ENSP00000376793.3	P01011-1
ENSG00000273259	ENST00000553947.1 link	n.*954C>T		non_coding_transcript_exon_variant	5/8	2		ENSP00000452367.2	G3V5I3
ENSG00000273259	ENST00000553947.1 link	n.*954C>T		3_prime_UTR_variant	5/8	2		ENSP00000452367.2	G3V5I3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.128C>T (p.T43I) alteration is located in exon 2 (coding exon 1) of the SERPINA3 gene. This alteration results from a C to T substitution at nucleotide position 128, causing the threonine (T) at amino acid position 43 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

0.32

DANN

Benign

0.92

DEOGEN2

Uncertain

0.50

D;D;.;D

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.23

T;.;T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.5

L;L;.;L

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.090

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.012

B;B;.;B

Vest4

0.18

MutPred

0.43

Gain of catalytic residue at D46 (P = 2e-04);Gain of catalytic residue at D46 (P = 2e-04);Gain of catalytic residue at D46 (P = 2e-04);Gain of catalytic residue at D46 (P = 2e-04);

MVP

0.63

MPC

0.011

ClinPred

0.074

GERP RS

-0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over