6-36961505-C-G

Position:

• chr6-36961505-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153370.3(PI16):​c.448C>G​(p.Leu150Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PI16 NM_153370.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

Genes affected

PI16 (HGNC:21245): (peptidase inhibitor 16) Predicted to enable peptidase inhibitor activity. Predicted to be involved in negative regulation of peptidase activity. Predicted to act upstream of or within negative regulation of cell growth involved in cardiac muscle cell development. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20993054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI16	NM_153370.3	c.448C>G	p.Leu150Val	missense_variant	3/7	ENST00000373674.4	NP_699201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI16	ENST00000373674.4	c.448C>G	p.Leu150Val	missense_variant	3/7	1	NM_153370.3	ENSP00000362778.3
PI16	ENST00000611814.4	c.448C>G	p.Leu150Val	missense_variant	4/8	5		ENSP00000478888.1
PI16	ENST00000647861.1	c.448C>G	p.Leu150Val	missense_variant	5/9			ENSP00000497550.1

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

May 24, 2023

The c.448C>G (p.L150V) alteration is located in exon 3 (coding exon 3) of the PI16 gene. This alteration results from a C to G substitution at nucleotide position 448, causing the leucine (L) at amino acid position 150 to be replaced by a valine (V). 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	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00058	T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.67	.;T;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.0	L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	.;.;N
REVEL	Benign	0.039
Sift	Benign	0.11	.;.;T
Sift4G	Benign	0.12	.;T;T
Polyphen		0.90	P;P;P
Vest4		0.37, 0.37
MutPred		0.48		Gain of methylation at K149 (P = 0.0406);Gain of methylation at K149 (P = 0.0406);Gain of methylation at K149 (P = 0.0406);
MVP		0.49
MPC		1.0
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.32

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: chr6-36929281;