NM_006217.6:c.980A>G

Variant names:

• chr3-167449387-T-C
• rs201533733
• NM_006217.6:c.980A>G

Variant summary

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

The NM_006217.6(SERPINI2):​c.980A>G​(p.Tyr327Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,146 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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.980A>G	p.Tyr327Cys	missense_variant	Exon 7 of 9	ENST00000264677.9	NP_006208.1
SERPINI2	NM_001012303.3	c.980A>G	p.Tyr327Cys	missense_variant	Exon 8 of 10		NP_001012303.2
SERPINI2	NM_001394327.1	c.980A>G	p.Tyr327Cys	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.980A>G	p.Tyr327Cys	missense_variant	Exon 7 of 9	1	NM_006217.6	ENSP00000264677.4
SERPINI2	ENST00000461846.5	c.980A>G	p.Tyr327Cys	missense_variant	Exon 7 of 9	1		ENSP00000417692.1
SERPINI2	ENST00000471111.5	c.980A>G	p.Tyr327Cys	missense_variant	Exon 6 of 8	1		ENSP00000419407.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;T;D;D;D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T;T;.;.;.
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Benign	1.3	L;.;L;L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.2	D;.;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0050	D;.;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D
Polyphen		0.99	D;.;D;D;D
Vest4		0.49
MutPred		0.55		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		0.39
MPC		0.73
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.35
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201533733; hg19: chr3-167167175;