chr15-24676197-C-T

Variant names:

• chr15-24676197-C-T
• rs756452322
• NM_018958.3:c.330C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018958.3(NPAP1):​c.330C>T​(p.His110His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NPAP1 NM_018958.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.626 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAP1	NM_018958.3	MANE Select	c.330C>T	p.His110His	synonymous	Exon 1 of 1	NP_061831.2	Q9NZP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAP1	ENST00000329468.5	TSL:6 MANE Select	c.330C>T	p.His110His	synonymous	Exon 1 of 1	ENSP00000333735.3	Q9NZP6
	ENSG00000286110	ENST00000650707.1		n.407+106069C>T		intron	N/A
	ENSG00000286110	ENST00000651136.1		n.1530+52092C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000505 AC: 1 AN: 198104 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000616

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401826 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 691982

African (AFR) AF: 0.00 AC: 0 AN: 31186

American (AMR) AF: 0.00 AC: 0 AN: 34706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21798

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39034

South Asian (SAS) AF: 0.00 AC: 0 AN: 76120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084714

Other (OTH) AF: 0.00 AC: 0 AN: 57680

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.63
PromoterAI		-0.012	Neutral

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: rs756452322; hg19: chr15-24921344;