NM_006217.6:c.203A>G

Variant names:

• chr3-167471632-T-C
• rs760162685
• NM_006217.6:c.203A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006217.6(SERPINI2):​c.203A>G​(p.Gln68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,586 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.154
• 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]

LOC105374197 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041606486).

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.203A>G	p.Gln68Arg	missense	Exon 2 of 9	NP_006208.1	O75830
	SERPINI2	NM_001012303.3		c.203A>G	p.Gln68Arg	missense	Exon 3 of 10	NP_001012303.2	O75830
	SERPINI2	NM_001394327.1		c.203A>G	p.Gln68Arg	missense	Exon 3 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.203A>G	p.Gln68Arg	missense	Exon 2 of 9	ENSP00000264677.4	O75830
	SERPINI2	ENST00000461846.5	TSL:1	c.203A>G	p.Gln68Arg	missense	Exon 2 of 9	ENSP00000417692.1	O75830
	SERPINI2	ENST00000471111.5	TSL:1	c.203A>G	p.Gln68Arg	missense	Exon 1 of 8	ENSP00000419407.1	O75830

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152160 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 251146 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461426 Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34 AN XY: 727012

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44650

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111758

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152160 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.3
DANN	Benign	0.67
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.47	N
PhyloP100		0.15
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.17
Sift	Benign	0.81	T
Sift4G	Benign	0.86	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.48		Gain of MoRF binding (P = 0.018)
MVP		0.56
MPC		0.17
ClinPred		0.010	T
GERP RS		2.0
PromoterAI		0.016	Neutral
Varity_R		0.088
gMVP		0.26
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs760162685; hg19: chr3-167189420;