chr11-90147491-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_005467.4(NAALAD2):c.356C>T(p.Ser119Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,608,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
NAALAD2
NM_005467.4 missense
NM_005467.4 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 7.38
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 152032Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152032
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000122 AC: 3AN: 246846 AF XY: 0.0000150 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
246846
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1456732Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 724394 show subpopulations
GnomAD4 exome
AF:
AC:
21
AN:
1456732
Hom.:
Cov.:
31
AF XY:
AC XY:
11
AN XY:
724394
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33252
American (AMR)
AF:
AC:
1
AN:
43494
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25872
East Asian (EAS)
AF:
AC:
6
AN:
39634
South Asian (SAS)
AF:
AC:
0
AN:
85318
European-Finnish (FIN)
AF:
AC:
0
AN:
53346
Middle Eastern (MID)
AF:
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
AC:
13
AN:
1109936
Other (OTH)
AF:
AC:
1
AN:
60144
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000132 AC: 2AN: 152032Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152032
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74258
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41368
American (AMR)
AF:
AC:
1
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
1
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4812
European-Finnish (FIN)
AF:
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 29, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.356C>T (p.S119L) alteration is located in exon 3 (coding exon 3) of the NAALAD2 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the serine (S) at amino acid position 119 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Pathogenic
DEOGEN2
Benign
T;.;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;D;D
Polyphen
D;.;D;.;.
Vest4
MutPred
Gain of catalytic residue at S119 (P = 0.0186);Gain of catalytic residue at S119 (P = 0.0186);Gain of catalytic residue at S119 (P = 0.0186);Gain of catalytic residue at S119 (P = 0.0186);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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