rs16976466

chr15-55680599-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173814.6(PRTG):c.706A>G(p.Thr236Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,562,626 control chromosomes in the GnomAD database, including 14,606 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2613 hom., cov: 31)
  • Exomes 𝑓: 0.12 (11993 hom.)
• Consequence: PRTG NM_173814.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

Genes affected

PRTG (HGNC:26373): (protogenin) This gene encodes a member of the immunoglobulin superfamily. The encoded transmembrane protein has been associated with the development of various tissues, especially neurogenesis. It has been suggested that this gene may be associated with attention deficit hyperactivity disorder (ADHD). [provided by RefSeq, Nov 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3857775E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRTG	NM_173814.6	c.706A>G	p.Thr236Ala	missense_variant	5/20	ENST00000389286.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRTG	ENST00000389286.9	c.706A>G	p.Thr236Ala	missense_variant	5/20	1	NM_173814.6	P1
	ENST00000561155.1	n.215T>C		splice_region_variant, non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24723 AN: 151814 Hom.: 2608 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.148 AC: 35305 AN: 238186 Hom.: 3516 AF XY: 0.150 AC XY: 19426 AN XY: 129692

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.0989

Gnomad NFE exome AF: 0.0946

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.116 AC: 163768 AN: 1410694 Hom.: 11993 Cov.: 31 AF XY: 0.119 AC XY: 83248 AN XY: 699526

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0935

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.163 AC: 24757 AN: 151932 Hom.: 2613 Cov.: 31 AF XY: 0.166 AC XY: 12317 AN XY: 74228

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.0961

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.146

Alfa AF: 0.115 Hom.: 2541

Bravo AF: 0.170

TwinsUK AF: 0.0928 AC: 344

ALSPAC AF: 0.0916 AC: 353

ESP6500AA AF: 0.276 AC: 1024

ESP6500EA AF: 0.0983 AC: 806

ExAC AF: 0.150 AC: 18175

Asia WGS AF: 0.252 AC: 871 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	9.7
Dann	Benign	0.86
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.00084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.048
Sift	Benign	0.55	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.088
ClinPred		0.0011	T
GERP RS		0.20
Varity_R		0.064
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16976466; hg19: chr15-55972797; COSMIC: COSV66837274; COSMIC: COSV66837274;