6-36959217-C-A

Variant names:

• chr6-36959217-C-A
• rs765919600
• NM_153370.3:c.244C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153370.3(PI16):​c.244C>A​(p.Arg82Ser) 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. 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. R82C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PI16 NM_153370.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 0 publications found

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]

ENSG00000305031 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18108407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153370.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI16	NM_153370.3	MANE Select	c.244C>A	p.Arg82Ser	missense	Exon 2 of 7	NP_699201.2	Q6UXB8-1
	PI16	NM_001199159.2		c.244C>A	p.Arg82Ser	missense	Exon 3 of 8	NP_001186088.1	Q6UXB8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI16	ENST00000373674.4	TSL:1 MANE Select	c.244C>A	p.Arg82Ser	missense	Exon 2 of 7	ENSP00000362778.3	Q6UXB8-1
	PI16	ENST00000611814.4	TSL:5	c.244C>A	p.Arg82Ser	missense	Exon 3 of 8	ENSP00000478888.1	Q6UXB8-1
	PI16	ENST00000647861.1		c.244C>A	p.Arg82Ser	missense	Exon 4 of 9	ENSP00000497550.1	Q6UXB8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.037
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.094	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.15
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.17
Sift	Benign	0.098	T
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.43		Gain of ubiquitination at K80 (P = 0.0376)
MVP		0.46
MPC		1.1
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.53
gMVP		0.65
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs765919600; hg19: chr6-36926993;