6-36954908-A-G

Position:

• chr6-36954908-A-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.148A>G​(p.Thr50Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T50P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PI16 NM_153370.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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=0.098864466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI16	NM_153370.3	c.148A>G	p.Thr50Ala	missense_variant	1/7	ENST00000373674.4	NP_699201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI16	ENST00000373674.4	c.148A>G	p.Thr50Ala	missense_variant	1/7	1	NM_153370.3	ENSP00000362778.3
PI16	ENST00000611814.4	c.148A>G	p.Thr50Ala	missense_variant	2/8	5		ENSP00000478888.1
PI16	ENST00000647861.1	c.148A>G	p.Thr50Ala	missense_variant	3/9			ENSP00000497550.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0041	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.10	.;T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.025	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	.;.;N
REVEL	Benign	0.045
Sift	Uncertain	0.027	.;.;D
Sift4G	Benign	0.082	.;T;T
Polyphen		0.076	B;B;B
Vest4		0.074
MutPred		0.38		Loss of phosphorylation at T50 (P = 0.0564);Loss of phosphorylation at T50 (P = 0.0564);Loss of phosphorylation at T50 (P = 0.0564);
MVP		0.15
MPC		0.31
ClinPred		0.22	T
GERP RS		3.7
Varity_R		0.063
gMVP		0.44

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: rs1405069; hg19: chr6-36922684;