11-90134704-C-T

Position:

• chr11-90134704-C-T

Variant summary

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

The NM_005467.4(NAALAD2):​c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,568,550 control chromosomes in the GnomAD database, including 119,655 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 0.45 (16292 hom., cov: 32)
  • Exomes 𝑓: 0.38 (103363 hom.)
• Consequence: NAALAD2 NM_005467.4 5_prime_UTR
• Scores: Splicing: ADA: 0.0004447
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

Genes affected

NAALAD2 (HGNC:14526): (N-acetylated alpha-linked acidic dipeptidase 2) This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

NAALAD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALAD2	NM_005467.4	c.-55C>T		5_prime_UTR_variant	1/19	ENST00000534061.6	NP_005458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALAD2	ENST00000534061	c.-55C>T		5_prime_UTR_variant	1/19	1	NM_005467.4	ENSP00000432481.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68118 AN: 151834 Hom.: 16259 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.375 AC: 531297 AN: 1416598 Hom.: 103363 Cov.: 23 AF XY: 0.376 AC XY: 266254 AN XY: 707428

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.449 AC: 68211 AN: 151952 Hom.: 16292 Cov.: 32 AF XY: 0.451 AC XY: 33480 AN XY: 74266

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.429

Alfa AF: 0.368 Hom.: 10491

Bravo AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00044
dbscSNV1_RF	Benign	0.022
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

Publications

LitVar

Other links and lift over

dbSNP: rs1892887; hg19: chr11-89867872; COSMIC: COSV58959618; COSMIC: COSV58959618;