Variant 14-94496560-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_001382267.1(SERPINA12):c.718A>G(p.Met240Val) variant causes a missense change. The variant allele was found at a frequency of 0.000391 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SERPINA12
NM_001382267.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.64

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05460182).

BP6

Variant 14-94496560-T-C is Benign according to our data. Variant chr14-94496560-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 730935.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA12	NM_001382267.1 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	3/5	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	3/5		NP_001291390.1	Q8IW75
SERPINA12	NM_173850.4 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	4/6		NP_776249.1	Q8IW75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINA12	ENST00000677451.1 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	3/5		NM_001382267.1	ENSP00000503935.1	Q8IW75
SERPINA12	ENST00000341228.2 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	4/6	1		ENSP00000342109.2	Q8IW75
SERPINA12	ENST00000556881.5 linkuse as main transcript	c.718A>G	p.Met240Val	missense_variant	3/5	1		ENSP00000451738.1	Q8IW75

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

218

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000617

AC:

155

AN:

251404

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000283

AC:

413

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

209

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00421

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152310

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00407

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000523

Hom.:

Bravo

AF:

0.00174

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000651

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.055

T;T

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

4.0

H;H

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.0

D;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.86

MVP

0.39

MPC

0.17

ClinPred

0.13

GERP RS

5.6

Varity_R

0.94

gMVP

0.70

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