chr15-24679516-T-C

Variant names:

• chr15-24679516-T-C
• rs12902137
• NM_018958.3:c.*178T>C

Variant summary

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

The NM_018958.3(NPAP1):​c.*178T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 618,436 control chromosomes in the GnomAD database, including 22,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5567 hom., cov: 33)
  • Exomes 𝑓: 0.27 (16992 hom.)
• Consequence: NPAP1 NM_018958.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 10 publications found

Genes affected

NPAP1 (HGNC:1190): (nuclear pore associated protein 1) This intronless retrogene is located in the Prader-Willi syndrome region on chromosome 15. This gene exhibits tissue-specific imprinting. Expression in adult testis and brain is biallelic, while expression in fetal brain is monoallelic and only from the paternal chromosome. The encoded protein is associated with the nuclear pore complex. [provided by RefSeq, Mar 2021]

ENSG00000286110 (HGNC:):

PWRN1 (HGNC:33235): (Prader-Willi region non-protein coding RNA 1) This gene is located in the Prader-Willi syndrome (PWS) region of chromosome 15, which is known to undergo imprinting. The transcript is believed to be non-coding. It is bi-allelically expressed in testis and kidney, but mono-allelically expressed from the paternal allele in brain. This gene is poly-adenylated and is known to undergo alternative splicing. Transcript variants may represent part of a complex imprinting center-SNURF-SNRPN transcription unit. The contribution of this gene to the PWS phenotype is unknown, but it has been suggested that it may play a role in establishing paternal imprinting in the PWS region, perhaps by maintaining the paternal allele in an open chromatin configuration. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018958.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAP1	NM_018958.3	MANE Select	c.*178T>C		3_prime_UTR	Exon 1 of 1	NP_061831.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAP1	ENST00000329468.5	TSL:6 MANE Select	c.*178T>C		3_prime_UTR	Exon 1 of 1	ENSP00000333735.3
	ENSG00000286110	ENST00000650707.1		n.407+109388T>C		intron	N/A
	ENSG00000286110	ENST00000651136.1		n.1530+55411T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40711 AN: 151988 Hom.: 5559 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.269 AC: 125491 AN: 466328 Hom.: 16992 Cov.: 4 AF XY: 0.269 AC XY: 66103 AN XY: 245396

African (AFR) AF: 0.262 AC: 3258 AN: 12458

American (AMR) AF: 0.271 AC: 4998 AN: 18458

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 3403 AN: 13592

East Asian (EAS) AF: 0.281 AC: 8711 AN: 30952

South Asian (SAS) AF: 0.271 AC: 12274 AN: 45210

European-Finnish (FIN) AF: 0.244 AC: 10707 AN: 43912

Middle Eastern (MID) AF: 0.266 AC: 565 AN: 2124

European-Non Finnish (NFE) AF: 0.272 AC: 74488 AN: 273528

Other (OTH) AF: 0.272 AC: 7087 AN: 26094

GnomAD4 genome AF: 0.268 AC: 40747 AN: 152108 Hom.: 5567 Cov.: 33 AF XY: 0.269 AC XY: 19970 AN XY: 74332

African (AFR) AF: 0.258 AC: 10730 AN: 41514

American (AMR) AF: 0.276 AC: 4219 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1540 AN: 5146

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2676 AN: 10568

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18229 AN: 67980

Other (OTH) AF: 0.273 AC: 576 AN: 2112

Alfa AF: 0.270 Hom.: 7659

Bravo AF: 0.271

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		-0.072
Mutation Taster		=100/0	polymorphism (auto)

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: rs12902137; hg19: chr15-24924663; COSMIC: COSV61507209;