Variant chr14-94487485-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382267.1(SERPINA12):c.1063A>G(p.Lys355Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SERPINA12
NM_001382267.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.171

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA12	NM_001382267.1 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	5/5	ENST00000677451.1
SERPINA12	NM_001304461.2 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	5/5
SERPINA12	NM_173850.4 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA12	ENST00000677451.1 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	5/5		NM_001382267.1	P1
SERPINA12	ENST00000341228.2 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	6/6	1		P1
SERPINA12	ENST00000556881.5 linkuse as main transcript	c.1063A>G	p.Lys355Glu	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247596

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000452

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Feb 28, 2024

The c.1063A>G (p.K355E) alteration is located in exon 6 (coding exon 4) of the SERPINA12 gene. This alteration results from a A to G substitution at nucleotide position 1063, causing the lysine (K) at amino acid position 355 to be replaced by a glutamic acid (E). 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

0.18

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.40

.;T

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Uncertain

-0.0028

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

0.96

D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.46

Sift

Benign

0.056

T;T

Sift4G

Benign

0.070

T;T

Polyphen

0.75

P;P

Vest4

0.33

MutPred

0.71

Loss of ubiquitination at K355 (P = 0.021);Loss of ubiquitination at K355 (P = 0.021);

MVP

0.48

MPC

0.053

ClinPred

0.39

GERP RS

1.9

Varity_R

0.45

gMVP

0.61

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