14-94489742-G-A

Variant names:

• chr14-94489742-G-A
• NM_001382267.1:c.931C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001382267.1(SERPINA12):​c.931C>T​(p.Leu311Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINA12 NM_001382267.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

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=0.04258573).
• BP6: Variant 14-94489742-G-A is Benign according to our data. Variant chr14-94489742-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3439894.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.931C>T	p.Leu311Phe	missense_variant	Exon 4 of 5	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2	c.931C>T	p.Leu311Phe	missense_variant	Exon 4 of 5		NP_001291390.1
SERPINA12	NM_173850.4	c.931C>T	p.Leu311Phe	missense_variant	Exon 5 of 6		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.931C>T	p.Leu311Phe	missense_variant	Exon 4 of 5		NM_001382267.1	ENSP00000503935.1
SERPINA12	ENST00000341228.2	c.931C>T	p.Leu311Phe	missense_variant	Exon 5 of 6	1		ENSP00000342109.2
SERPINA12	ENST00000556881.5	c.931C>T	p.Leu311Phe	missense_variant	Exon 4 of 5	1		ENSP00000451738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.62
DANN	Benign	0.86
DEOGEN2	Benign	0.049	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.60	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.59		Gain of catalytic residue at R310 (P = 2e-04);Gain of catalytic residue at R310 (P = 2e-04);
MVP		0.030
MPC		0.021
ClinPred		0.066	T
GERP RS		3.0
Varity_R		0.19
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94956079;