rs1973972

Variant names:

• chr10-109891375-T-A
• rs1973972
• NM_020383.4:c.415+347A>T

Variant summary

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

The NM_020383.4(XPNPEP1):​c.415+347A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 169,540 control chromosomes in the GnomAD database, including 7,753 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 0.30 (7054 hom., cov: 32)
  • Exomes 𝑓: 0.27 (699 hom.)
• Consequence: XPNPEP1 NM_020383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 5 publications found

Genes affected

XPNPEP1 (HGNC:12822): (X-prolyl aminopeptidase 1) This gene encodes the cytosolic form of a metalloaminopeptidase that catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. The gene product may play a role in degradation and maturation of tachykinins, neuropeptides, and peptide hormones. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Nov 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP1	NM_020383.4	c.415+347A>T		intron_variant	Intron 5 of 20	ENST00000502935.6	NP_065116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPNPEP1	ENST00000502935.6	c.415+347A>T		intron_variant	Intron 5 of 20	1	NM_020383.4	ENSP00000421566.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44981 AN: 151974 Hom.: 7033 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.266 AC: 4634 AN: 17446 Hom.: 699 Cov.: 0 AF XY: 0.262 AC XY: 2326 AN XY: 8866

African (AFR) AF: 0.331 AC: 244 AN: 738

American (AMR) AF: 0.483 AC: 305 AN: 632

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 161 AN: 760

East Asian (EAS) AF: 0.371 AC: 432 AN: 1164

South Asian (SAS) AF: 0.235 AC: 48 AN: 204

European-Finnish (FIN) AF: 0.227 AC: 173 AN: 762

Middle Eastern (MID) AF: 0.283 AC: 26 AN: 92

European-Non Finnish (NFE) AF: 0.245 AC: 2915 AN: 11878

Other (OTH) AF: 0.271 AC: 330 AN: 1216

GnomAD4 genome AF: 0.296 AC: 45049 AN: 152094 Hom.: 7054 Cov.: 32 AF XY: 0.297 AC XY: 22054 AN XY: 74344

African (AFR) AF: 0.337 AC: 13964 AN: 41464

American (AMR) AF: 0.458 AC: 6998 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1850 AN: 5166

South Asian (SAS) AF: 0.228 AC: 1102 AN: 4826

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10592

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17005 AN: 67978

Other (OTH) AF: 0.313 AC: 659 AN: 2108

Alfa AF: 0.275 Hom.: 780

Bravo AF: 0.319

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.019
DANN	Benign	0.42
PhyloP100		-1.8
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: rs1973972; hg19: chr10-111651133;