Variant 14-94489693-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001382267.1(SERPINA12):c.980G>A(p.Gly327Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,614,154 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 19 hom. )

Consequence

SERPINA12
NM_001382267.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

SERPINA12 (HGNC:18359): (serpin family A member 12) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within negative regulation of gluconeogenesis; positive regulation of signal transduction; and regulation of lipid metabolic process. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023187011).

BP6

Variant 14-94489693-C-T is Benign according to our data. Variant chr14-94489693-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067196.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA12	NM_001382267.1 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	4/5	ENST00000677451.1
SERPINA12	NM_001304461.2 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	4/5
SERPINA12	NM_173850.4 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA12	ENST00000677451.1 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	4/5		NM_001382267.1	P1
SERPINA12	ENST00000341228.2 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	5/6	1		P1
SERPINA12	ENST00000556881.5 linkuse as main transcript	c.980G>A	p.Gly327Asp	missense_variant	4/5	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00328

AC:

826

AN:

251454

Hom.:

AF XY:

0.00318

AC XY:

432

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0191

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00205

AC:

2995

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1468

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152280

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00127

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00312

AC:

379

EpiCase

AF:

0.00229

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

SERPINA12: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.40

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

MetaRNN

Benign

0.023

T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.9

H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.3

D;D

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

1.0

D;D

Vest4

0.81

MVP

0.77

MPC

0.18

ClinPred

0.17

GERP RS

5.2

Varity_R

0.77

gMVP

0.71

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