Variant rs61757459 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001382267.1(SERPINA12):c.631C>T(p.Arg211Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00714 in 1,600,876 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 53 hom. )

Consequence

SERPINA12
NM_001382267.1 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 4.32

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 -6 ACMG points.

BP6

Variant 14-94497767-G-A is Benign according to our data. Variant chr14-94497767-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2574603.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINA12	NM_001382267.1 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	2/5	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	2/5		NP_001291390.1
SERPINA12	NM_173850.4 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	3/6		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINA12	ENST00000677451.1 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	2/5		NM_001382267.1	ENSP00000503935	P1
SERPINA12	ENST00000341228.2 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	3/6	1		ENSP00000342109	P1
SERPINA12	ENST00000556881.5 linkuse as main transcript	c.631C>T	p.Arg211Ter	stop_gained	2/5	1		ENSP00000451738	P1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

753

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00784

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00510

AC:

1235

AN:

242086

Hom.:

AF XY:

0.00498

AC XY:

651

AN XY:

130694

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.000211

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.000462

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00750

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00737

AC:

10680

AN:

1448656

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

5082

AN XY:

719408

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.000352

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000810

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00860

Gnomad4 OTH exome

AF:

0.00509

GnomAD4 genome

AF:

0.00495

AC:

753

AN:

152220

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

337

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.00784

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00688

Hom.:

Bravo

AF:

0.00468

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00526

AC:

638

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary palmoplantar keratoderma, Gamborg-Nielsen type

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

Institute for Human Genetics, University Medical Center Freiburg

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SERPINA12: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.89

MutationTaster

Benign

1.0

A;A

Vest4

0.52

GERP RS

5.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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