chr3-167471669-G-A

Position:

• chr3-167471669-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006217.6(SERPINI2):​c.166C>T​(p.Leu56Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINI2 NM_006217.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI2	NM_006217.6	c.166C>T	p.Leu56Phe	missense_variant	2/9	ENST00000264677.9
LOC105374197	XR_924683.3	n.127+548G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI2	ENST00000264677.9	c.166C>T	p.Leu56Phe	missense_variant	2/9	1	NM_006217.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.166C>T (p.L56F) alteration is located in exon 2 (coding exon 1) of the SERPINI2 gene. This alteration results from a C to T substitution at nucleotide position 166, causing the leucine (L) at amino acid position 56 to be replaced by a phenylalanine (F). 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	0.32
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.54	D;T;D;D;D;.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T;T;.;.;.;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Uncertain	2.2	M;.;M;M;M;.;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D;.;D;D;D;D;D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0050	D;.;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;.
Polyphen		1.0	D;.;D;D;D;.;.
Vest4		0.65
MutPred		0.85		Loss of MoRF binding (P = 0.2758);.;Loss of MoRF binding (P = 0.2758);Loss of MoRF binding (P = 0.2758);Loss of MoRF binding (P = 0.2758);Loss of MoRF binding (P = 0.2758);Loss of MoRF binding (P = 0.2758);
MVP		0.83
MPC		0.71
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.57
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-167189457;