11-90134704-C-T

Variant names:

• chr11-90134704-C-T
• rs1892887
• NM_005467.4:c.-55C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005467.4. 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
	NAALAD2	NM_005467.4	MANE Select	c.-55C>T		5_prime_UTR	Exon 1 of 19	NP_005458.1	Q9Y3Q0-1
	NAALAD2	NM_001300930.2		c.-55C>T		5_prime_UTR	Exon 1 of 18	NP_001287859.1	J3KNJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALAD2	ENST00000534061.6	TSL:1 MANE Select	c.-55C>T		5_prime_UTR	Exon 1 of 19	ENSP00000432481.1	Q9Y3Q0-1
	NAALAD2	ENST00000524501.1	TSL:1	n.10C>T		non_coding_transcript_exon	Exon 1 of 10
	NAALAD2	ENST00000529090.5	TSL:1	n.41C>T		non_coding_transcript_exon	Exon 1 of 7

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

African (AFR) AF: 0.625 AC: 20327 AN: 32528

American (AMR) AF: 0.590 AC: 26276 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10195 AN: 25842

East Asian (EAS) AF: 0.420 AC: 16562 AN: 39442

South Asian (SAS) AF: 0.493 AC: 42040 AN: 85194

European-Finnish (FIN) AF: 0.398 AC: 21110 AN: 53044

Middle Eastern (MID) AF: 0.395 AC: 1669 AN: 4228

European-Non Finnish (NFE) AF: 0.345 AC: 370691 AN: 1073060

Other (OTH) AF: 0.382 AC: 22427 AN: 58760

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

African (AFR) AF: 0.612 AC: 25354 AN: 41462

American (AMR) AF: 0.501 AC: 7656 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1320 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2173 AN: 5130

South Asian (SAS) AF: 0.493 AC: 2368 AN: 4806

European-Finnish (FIN) AF: 0.394 AC: 4163 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23835 AN: 67944

Other (OTH) AF: 0.429 AC: 904 AN: 2108

Alfa AF: 0.382 Hom.: 14986

Bravo AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.24
PromoterAI		-0.049	Neutral
Mutation Taster		=293/7	polymorphism (auto)

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

Other links and lift over

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