Variant 11-90163289-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005467.4(NAALAD2):c.1076-21C>T variant causes a intron 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
NM_005467.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NAALAD2	NM_005467.4 link	c.1076-21C>T		intron_variant		ENST00000534061.6	NP_005458.1	Q9Y3Q0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALAD2	ENST00000534061.6 link	c.1076-21C>T		intron_variant		1	NM_005467.4	ENSP00000432481.1		Q9Y3Q0-1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94734

AN:

151840

Hom.:

31323

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.571

AC:

136994

AN:

240094

Hom.:

40484

AF XY:

0.563

AC XY:

73352

AN XY:

130322

show subpopulations

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 SAS exome

AF:

0.610

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.:

AF XY:

0.532

AC XY:

382524

AN XY:

718770

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.687

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.624

AC:

94851

AN:

151958

Hom.:

31372

Cov.:

AF XY:

0.625

AC XY:

46412

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.854

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.605

Alfa

AF:

0.526

Hom.:

17786

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over