16-83990615-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_019065.3(NECAB2):c.581A>T(p.Gln194Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
NECAB2
NM_019065.3 missense
NM_019065.3 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 9.15
Genes affected
NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.755
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECAB2 | NM_019065.3 | c.581A>T | p.Gln194Leu | missense_variant | 6/13 | ENST00000305202.9 | |
NECAB2 | NM_001329748.1 | c.581A>T | p.Gln194Leu | missense_variant | 6/12 | ||
NECAB2 | NM_001329749.2 | c.332A>T | p.Gln111Leu | missense_variant | 5/12 | ||
NECAB2 | XM_047434240.1 | c.332A>T | p.Gln111Leu | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECAB2 | ENST00000305202.9 | c.581A>T | p.Gln194Leu | missense_variant | 6/13 | 1 | NM_019065.3 | P1 | |
NECAB2 | ENST00000565691.5 | c.332A>T | p.Gln111Leu | missense_variant | 4/11 | 1 | |||
NECAB2 | ENST00000566836.1 | c.254A>T | p.Gln85Leu | missense_variant | 4/7 | 5 | |||
NECAB2 | ENST00000681513.1 | n.986A>T | non_coding_transcript_exon_variant | 6/13 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249232Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134870
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727230
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2024 | The c.581A>T (p.Q194L) alteration is located in exon 6 (coding exon 6) of the NECAB2 gene. This alteration results from a A to T substitution at nucleotide position 581, causing the glutamine (Q) at amino acid position 194 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
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of disorder (P = 0.099);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at