3-167467279-T-A

Variant names:

• chr3-167467279-T-A
• rs746372943
• NM_006217.6:c.254A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E85G) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006217.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI2	NM_006217.6	MANE Select	c.254A>T	p.Glu85Val	missense	Exon 3 of 9	NP_006208.1	O75830
	SERPINI2	NM_001012303.3		c.254A>T	p.Glu85Val	missense	Exon 4 of 10	NP_001012303.2	O75830
	SERPINI2	NM_001394327.1		c.254A>T	p.Glu85Val	missense	Exon 4 of 10	NP_001381256.1	O75830

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI2	ENST00000264677.9	TSL:1 MANE Select	c.254A>T	p.Glu85Val	missense	Exon 3 of 9	ENSP00000264677.4	O75830
	SERPINI2	ENST00000461846.5	TSL:1	c.254A>T	p.Glu85Val	missense	Exon 3 of 9	ENSP00000417692.1	O75830
	SERPINI2	ENST00000471111.5	TSL:1	c.254A>T	p.Glu85Val	missense	Exon 2 of 8	ENSP00000419407.1	O75830

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

African (AFR) AF: 0.00 AC: 0 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 85516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107648

Other (OTH) AF: 0.00 AC: 0 AN: 59992

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.11
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.33	N
REVEL	Uncertain	0.52
Sift	Benign	0.042	D
Sift4G	Benign	0.097	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.54		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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs746372943; hg19: chr3-167185067;