rs1405069

Variant names:

• chr6-36954908-A-C
• rs1405069
• NM_153370.3:c.148A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-36954908-A-C
• chr6-36954908-A-G
• chr6-36954908-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153370.3(PI16):​c.148A>C​(p.Thr50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,844 control chromosomes in the GnomAD database, including 176,539 homozygotes. 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. T50M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.53 (22417 hom., cov: 31)
  • Exomes 𝑓: 0.46 (154122 hom.)
• Consequence: PI16 NM_153370.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 37 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6780249E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI16	NM_153370.3	c.148A>C	p.Thr50Pro	missense_variant	Exon 1 of 7	ENST00000373674.4	NP_699201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI16	ENST00000373674.4	c.148A>C	p.Thr50Pro	missense_variant	Exon 1 of 7	1	NM_153370.3	ENSP00000362778.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80257 AN: 151800 Hom.: 22373 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.508

GnomAD2 exomes AF: 0.478 AC: 118591 AN: 248036 AF XY: 0.465

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.466

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.455 AC: 665095 AN: 1460926 Hom.: 154122 Cov.: 52 AF XY: 0.452 AC XY: 328609 AN XY: 726776

African (AFR) AF: 0.713 AC: 23836 AN: 33450

American (AMR) AF: 0.601 AC: 26856 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10681 AN: 26132

East Asian (EAS) AF: 0.508 AC: 20164 AN: 39684

South Asian (SAS) AF: 0.398 AC: 34298 AN: 86194

European-Finnish (FIN) AF: 0.425 AC: 22672 AN: 53360

Middle Eastern (MID) AF: 0.473 AC: 2480 AN: 5240

European-Non Finnish (NFE) AF: 0.446 AC: 496109 AN: 1111860

Other (OTH) AF: 0.464 AC: 27999 AN: 60324

GnomAD4 genome AF: 0.529 AC: 80360 AN: 151918 Hom.: 22417 Cov.: 31 AF XY: 0.526 AC XY: 39074 AN XY: 74242

African (AFR) AF: 0.703 AC: 29133 AN: 41460

American (AMR) AF: 0.584 AC: 8920 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2467 AN: 5136

South Asian (SAS) AF: 0.401 AC: 1929 AN: 4814

European-Finnish (FIN) AF: 0.425 AC: 4482 AN: 10536

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.448 AC: 30426 AN: 67924

Other (OTH) AF: 0.504 AC: 1062 AN: 2108

Alfa AF: 0.471 Hom.: 54635

Bravo AF: 0.552

TwinsUK AF: 0.454 AC: 1685

ESP6500AA AF: 0.693 AC: 3052

ESP6500EA AF: 0.446 AC: 3833

ExAC AF: 0.473 AC: 57480

Asia WGS AF: 0.410 AC: 1426 AN: 3478

EpiCase AF: 0.446

EpiControl AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.034
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.85
DANN	Benign	0.14
DEOGEN2	Benign	0.00043	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
LIST_S2	Benign	0.0	.;T;.
MetaRNN	Benign	0.0000027	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.3	N;N;N
PhyloP100		0.39
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.0	.;.;N
Sift	Pathogenic	0.0	.;.;T
Sift4G	Pathogenic	0.0	.;T;T
Vest4		0.0
ClinPred		0.0020	T
GERP RS		3.7
PromoterAI		-0.043	Neutral
Varity_R		0.075
gMVP		0.54
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1405069; hg19: chr6-36922684; COSMIC: COSV65448502;