14-94487364-T-G

Position:

• chr14-94487364-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382267.1(SERPINA12):​c.1184A>C​(p.Tyr395Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINA12 NM_001382267.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.54

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11963692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA12	NM_001382267.1	c.1184A>C	p.Tyr395Ser	missense_variant	5/5	ENST00000677451.1	NP_001369196.1
SERPINA12	NM_001304461.2	c.1184A>C	p.Tyr395Ser	missense_variant	5/5		NP_001291390.1
SERPINA12	NM_173850.4	c.1184A>C	p.Tyr395Ser	missense_variant	6/6		NP_776249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA12	ENST00000677451.1	c.1184A>C	p.Tyr395Ser	missense_variant	5/5		NM_001382267.1	ENSP00000503935.1
SERPINA12	ENST00000341228.2	c.1184A>C	p.Tyr395Ser	missense_variant	6/6	1		ENSP00000342109.2
SERPINA12	ENST00000556881.5	c.1184A>C	p.Tyr395Ser	missense_variant	5/5	1		ENSP00000451738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.1184A>C (p.Y395S) alteration is located in exon 6 (coding exon 4) of the SERPINA12 gene. This alteration results from a A to C substitution at nucleotide position 1184, causing the tyrosine (Y) at amino acid position 395 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.041
DANN	Benign	0.65
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.37	.;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.30
Sift	Benign	0.15	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.16	B;B
Vest4		0.20
MutPred		0.43		Gain of catalytic residue at L391 (P = 0);Gain of catalytic residue at L391 (P = 0);
MVP		0.030
MPC		0.025
ClinPred		0.28	T
GERP RS		-11
Varity_R		0.39
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94953701;