NM_006217.6:c.995C>T

Variant names:

• chr3-167449372-G-A
• rs201666797
• NM_006217.6:c.995C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006217.6(SERPINI2):​c.995C>T​(p.Thr332Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,611,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.727
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016834944).
• BP6: Variant 3-167449372-G-A is Benign according to our data. Variant chr3-167449372-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3440091.Status of the report is criteria_provided_single_submitter, 1 stars.

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.995C>T	p.Thr332Met	missense	Exon 7 of 9	NP_006208.1	O75830
	SERPINI2	NM_001012303.3		c.995C>T	p.Thr332Met	missense	Exon 8 of 10	NP_001012303.2	O75830
	SERPINI2	NM_001394327.1		c.995C>T	p.Thr332Met	missense	Exon 8 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.995C>T	p.Thr332Met	missense	Exon 7 of 9	ENSP00000264677.4	O75830
	SERPINI2	ENST00000461846.5	TSL:1	c.995C>T	p.Thr332Met	missense	Exon 7 of 9	ENSP00000417692.1	O75830
	SERPINI2	ENST00000471111.5	TSL:1	c.995C>T	p.Thr332Met	missense	Exon 6 of 8	ENSP00000419407.1	O75830

Frequencies

GnomAD3 genomes AF: 0.0000792 AC: 12 AN: 151572 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000964

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000151 AC: 38 AN: 250882 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000740 AC: 108 AN: 1460040 Hom.: 0 Cov.: 30 AF XY: 0.0000702 AC XY: 51 AN XY: 726488

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.000872 AC: 39 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86190

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1110778

Other (OTH) AF: 0.0000829 AC: 5 AN: 60332

GnomAD4 genome AF: 0.0000792 AC: 12 AN: 151572 Hom.: 0 Cov.: 32 AF XY: 0.0000676 AC XY: 5 AN XY: 73948

African (AFR) AF: 0.0000485 AC: 2 AN: 41232

American (AMR) AF: 0.000329 AC: 5 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.0000964 AC: 1 AN: 10376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000912 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.27
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.73
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.12
Sift	Benign	0.62	T
Sift4G	Benign	0.37	T
Polyphen		0.0030	B
Vest4		0.067
MutPred		0.46		Gain of catalytic residue at V328 (P = 0.0203)
MVP		0.15
MPC		0.17
ClinPred		0.028	T
GERP RS		2.0
Varity_R		0.025
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201666797; hg19: chr3-167167160; COSMIC: COSV52986468; COSMIC: COSV52986468;