3-167471713-T-A

Position:

• chr3-167471713-T-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.122A>T​(p.His41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 1.33

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24127096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI2	NM_006217.6	c.122A>T	p.His41Leu	missense_variant	2/9	ENST00000264677.9
LOC105374197	XR_924683.3	n.127+592T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI2	ENST00000264677.9	c.122A>T	p.His41Leu	missense_variant	2/9	1	NM_006217.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

May 09, 2022

The c.122A>T (p.H41L) alteration is located in exon 2 (coding exon 1) of the SERPINI2 gene. This alteration results from a A to T substitution at nucleotide position 122, causing the histidine (H) at amino acid position 41 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.36	T;T;T;T;T;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.47	T;T;.;.;.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.4	L;.;L;L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.7	D;.;D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.31	T;.;T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T;.
Polyphen		0.41	B;.;B;B;B;.;.
Vest4		0.32
MutPred		0.46		Loss of methylation at K42 (P = 0.053);.;Loss of methylation at K42 (P = 0.053);Loss of methylation at K42 (P = 0.053);Loss of methylation at K42 (P = 0.053);Loss of methylation at K42 (P = 0.053);Loss of methylation at K42 (P = 0.053);
MVP		0.64
MPC		0.35
ClinPred		0.39	T
GERP RS		4.5
Varity_R		0.23
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr3-167189501;