Variant rs1445192595 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM2PP3_StrongBP6_Moderate

The NM_000295.5(SERPINA1):c.654G>T(p.Trp218Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SERPINA1
NM_000295.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.95

Variant links:

Genes affected

SERPINA1 (HGNC:8941): (serpin family A member 1) The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

SERPINA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.983

BP6

Variant 14-94381134-C-A is Benign according to our data. Variant chr14-94381134-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 626302.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA1	NM_000295.5 link	c.654G>T	p.Trp218Cys	missense_variant	3/5	ENST00000393087.9	NP_000286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA1	ENST00000393087.9 link	c.654G>T	p.Trp218Cys	missense_variant	3/5	1	NM_000295.5	ENSP00000376802.4		P01009-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726272

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Alpha-1-antitrypsin deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

HerediLab, Inc.

Oct 24, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;D;D;D;D;D;D;D;D;.

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;.;.;D;.;.;.;.;.;D

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.4

H;H;H;H;H;H;H;H;H;H

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-12

D;D;D;D;D;.;D;D;D;D

REVEL

Pathogenic

0.76

Sift

Benign

0.038

D;D;D;D;D;.;D;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D;D;.;D;D;D;D

Polyphen

0.96

D;D;D;D;D;D;D;D;D;D

Vest4

0.80

MutPred

0.82

Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);Gain of catalytic residue at K215 (P = 0.0047);

MVP

0.97

MPC

0.37

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.89

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

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