3-167471666-C-T

Variant names:

• chr3-167471666-C-T
• rs764938775
• NM_006217.6:c.169G>A

Variant summary

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

The NM_006217.6(SERPINI2):​c.169G>A​(p.Glu57Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

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

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.169G>A	p.Glu57Lys	missense_variant	Exon 2 of 9	ENST00000264677.9	NP_006208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI2	ENST00000264677.9	c.169G>A	p.Glu57Lys	missense_variant	Exon 2 of 9	1	NM_006217.6	ENSP00000264677.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251098 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135698

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169G>A (p.E57K) alteration is located in exon 2 (coding exon 1) of the SERPINI2 gene. This alteration results from a G to A substitution at nucleotide position 169, causing the glutamic acid (E) at amino acid position 57 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;T;T;T;.;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;T;.;.;.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.0	N;.;N;N;N;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.080	N;.;N;N;N;N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D;.;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;.
Polyphen		0.048	B;.;B;B;B;.;.
Vest4		0.29
MutPred		0.74		Gain of MoRF binding (P = 0.0034);.;Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);
MVP		0.77
MPC		0.23
ClinPred		0.78	D
GERP RS		5.7
Varity_R		0.52
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs764938775; hg19: chr3-167189454; COSMIC: COSV52984285;