chr15-55680599-T-C

Variant names:

• chr15-55680599-T-C
• rs16976466
• NM_173814.6:c.706A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 publications found

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]

ENSG00000259180 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173814.6. 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
	PRTG	NM_173814.6	MANE Select	c.706A>G	p.Thr236Ala	missense	Exon 5 of 20	NP_776175.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRTG	ENST00000389286.9	TSL:1 MANE Select	c.706A>G	p.Thr236Ala	missense	Exon 5 of 20	ENSP00000373937.4	Q2VWP7
	ENSG00000259180	ENST00000561155.1	TSL:3	n.215T>C		splice_region non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.148 AC: 35305 AN: 238186 AF XY: 0.150

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 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

African (AFR) AF: 0.291 AC: 9449 AN: 32480

American (AMR) AF: 0.120 AC: 5107 AN: 42576

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4481 AN: 25002

East Asian (EAS) AF: 0.291 AC: 11213 AN: 38566

South Asian (SAS) AF: 0.237 AC: 17339 AN: 73304

European-Finnish (FIN) AF: 0.101 AC: 5121 AN: 50744

Middle Eastern (MID) AF: 0.202 AC: 1129 AN: 5580

European-Non Finnish (NFE) AF: 0.0935 AC: 101367 AN: 1084408

Other (OTH) AF: 0.148 AC: 8562 AN: 58034

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

African (AFR) AF: 0.276 AC: 11444 AN: 41414

American (AMR) AF: 0.131 AC: 1992 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1622 AN: 5168

South Asian (SAS) AF: 0.249 AC: 1197 AN: 4812

European-Finnish (FIN) AF: 0.0961 AC: 1015 AN: 10560

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.0945 AC: 6421 AN: 67948

Other (OTH) AF: 0.146 AC: 309 AN: 2110

Alfa AF: 0.127 Hom.: 4765

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 v4.9

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
PhyloP100		0.15
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16976466; hg19: chr15-55972797; COSMIC: COSV66837274; COSMIC: COSV66837274;