11-90163289-C-T

Variant names:

• chr11-90163289-C-T
• rs489009
• ENST00000532691.1:n.798C>T

Variant summary

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

The ENST00000532691.1(NAALAD2):​n.798C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,596,804 control chromosomes in the GnomAD database, including 238,578 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 0.62 (31372 hom., cov: 32)
  • Exomes 𝑓: 0.53 (207206 hom.)
• Consequence: NAALAD2 ENST00000532691.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 12 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALAD2	NM_005467.4	c.1076-21C>T		intron_variant	Intron 9 of 18	ENST00000534061.6	NP_005458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALAD2	ENST00000534061.6	c.1076-21C>T		intron_variant	Intron 9 of 18	1	NM_005467.4	ENSP00000432481.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94734 AN: 151840 Hom.: 31323 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.602

GnomAD2 exomes AF: 0.571 AC: 136994 AN: 240094 AF XY: 0.563

Gnomad AFR exome AF: 0.863

Gnomad AMR exome AF: 0.690

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.460

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.531 AC: 767515 AN: 1444846 Hom.: 207206 Cov.: 33 AF XY: 0.532 AC XY: 382524 AN XY: 718770

African (AFR) AF: 0.864 AC: 27984 AN: 32372

American (AMR) AF: 0.687 AC: 28170 AN: 41012

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13302 AN: 25354

East Asian (EAS) AF: 0.479 AC: 18976 AN: 39634

South Asian (SAS) AF: 0.613 AC: 51188 AN: 83528

European-Finnish (FIN) AF: 0.538 AC: 28603 AN: 53184

Middle Eastern (MID) AF: 0.556 AC: 3147 AN: 5660

European-Non Finnish (NFE) AF: 0.511 AC: 563968 AN: 1104450

Other (OTH) AF: 0.539 AC: 32177 AN: 59652

GnomAD4 genome AF: 0.624 AC: 94851 AN: 151958 Hom.: 31372 Cov.: 32 AF XY: 0.625 AC XY: 46412 AN XY: 74238

African (AFR) AF: 0.854 AC: 35449 AN: 41490

American (AMR) AF: 0.646 AC: 9857 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2416 AN: 5148

South Asian (SAS) AF: 0.615 AC: 2960 AN: 4814

European-Finnish (FIN) AF: 0.544 AC: 5737 AN: 10542

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34756 AN: 67910

Other (OTH) AF: 0.605 AC: 1276 AN: 2110

Alfa AF: 0.555 Hom.: 33397

Bravo AF: 0.643

Asia WGS AF: 0.594 AC: 2064 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.081
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: rs489009; hg19: chr11-89896457; COSMIC: COSV58959658; COSMIC: COSV58959658;