3-167449372-G-T

Variant names:

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

Variant summary

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

The NM_006217.6(SERPINI2):​c.995C>A​(p.Thr332Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13125041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINI2	NM_006217.6	c.995C>A	p.Thr332Lys	missense_variant	Exon 7 of 9	ENST00000264677.9	NP_006208.1
SERPINI2	NM_001012303.3	c.995C>A	p.Thr332Lys	missense_variant	Exon 8 of 10		NP_001012303.2
SERPINI2	NM_001394327.1	c.995C>A	p.Thr332Lys	missense_variant	Exon 8 of 10		NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI2	ENST00000264677.9	c.995C>A	p.Thr332Lys	missense_variant	Exon 7 of 9	1	NM_006217.6	ENSP00000264677.4
SERPINI2	ENST00000461846.5	c.995C>A	p.Thr332Lys	missense_variant	Exon 7 of 9	1		ENSP00000417692.1
SERPINI2	ENST00000471111.5	c.995C>A	p.Thr332Lys	missense_variant	Exon 6 of 8	1		ENSP00000419407.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151572 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460046 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151572 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73948

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.19	T;T;T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.33	T;T;.;.;.
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	-0.090	N;.;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;.;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D;.;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.17	B;.;B;B;B
Vest4		0.17
MutPred		0.71		Gain of glycosylation at Y327 (P = 0.032);.;Gain of glycosylation at Y327 (P = 0.032);Gain of glycosylation at Y327 (P = 0.032);Gain of glycosylation at Y327 (P = 0.032);
MVP		0.14
MPC		0.20
ClinPred		0.35	T
GERP RS		2.0
Varity_R		0.17
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs201666797; hg19: chr3-167167160;