14-94592125-A-G

Variant names:

• chr14-94592125-A-G
• NM_000624.6:c.1107A>G

Variant summary

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

The NM_000624.6(SERPINA5):​c.1107A>G​(p.Ile369Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERPINA5 NM_000624.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

SERPINA5 (HGNC:8723): (serpin family A member 5) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]

ENSG00000273259 (HGNC:):

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=0.10879585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA5	NM_000624.6	c.1107A>G	p.Ile369Met	missense_variant	Exon 6 of 6	ENST00000329597.12	NP_000615.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA5	ENST00000329597.12	c.1107A>G	p.Ile369Met	missense_variant	Exon 6 of 6	1	NM_000624.6	ENSP00000333203.7
ENSG00000273259	ENST00000553947.1	n.66A>G		non_coding_transcript_exon_variant	Exon 1 of 8	2		ENSP00000452367.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.3
DANN	Benign	0.67
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.20	.;T;.;.
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.7	L;L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.050	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.0070	B;B;B;B
Vest4		0.081
MutPred		0.31		Gain of catalytic residue at I369 (P = 0.0014);Gain of catalytic residue at I369 (P = 0.0014);Gain of catalytic residue at I369 (P = 0.0014);Gain of catalytic residue at I369 (P = 0.0014);
MVP		0.64
MPC		0.012
ClinPred		0.041	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-95058462; COSMIC: COSV61574741; COSMIC: COSV61574741;