chr3-167467279-T-A

Variant names:

• chr3-167467279-T-A
• NM_006217.6:c.254A>T

Variant summary

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

The NM_006217.6(SERPINI2):​c.254A>T​(p.Glu85Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,453,128 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

Genes affected

SERPINI2 (HGNC:8945): (serpin family I member 2) The gene encodes a member of a family of proteins that acts as inhibitors of serine proteases. These proteins function in the regulation of a variety of physiological processes, including coagulation, fibrinolysis, development, malignancy, and inflammation. Expression of the encoded protein may be downregulated during pancreatic carcinogenesis. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

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 rank	MANE	Protein	UniProt
SERPINI2	NM_006217.6	c.254A>T	p.Glu85Val	missense_variant	Exon 3 of 9	ENST00000264677.9	NP_006208.1
SERPINI2	NM_001012303.3	c.254A>T	p.Glu85Val	missense_variant	Exon 4 of 10		NP_001012303.2
SERPINI2	NM_001394327.1	c.254A>T	p.Glu85Val	missense_variant	Exon 4 of 10		NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI2	ENST00000264677.9	c.254A>T	p.Glu85Val	missense_variant	Exon 3 of 9	1	NM_006217.6	ENSP00000264677.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453128 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723214

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: 0.00000361

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	0.18
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T;T;T;T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;.;.;.;T
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.55	N;.;N;N;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.33	N;.;N;N;N;N
REVEL	Uncertain	0.52
Sift	Benign	0.042	D;.;D;D;D;D
Sift4G	Benign	0.097	T;T;T;T;T;T
Polyphen		1.0	D;.;D;D;D;.
Vest4		0.76
MutPred		0.54		Loss of disorder (P = 0.0085);.;Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);
MVP		0.81
MPC		0.61
ClinPred		0.85	D
GERP RS		5.4
Varity_R		0.37
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.47		Position offset: 6

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: chr3-167185067;