chr16-83990531-C-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.497C>T(p.Thr166Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,134 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
NECAB2
NM_019065.3 missense
NM_019065.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 7.78
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, 0.761
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECAB2 | NM_019065.3 | c.497C>T | p.Thr166Ile | missense_variant | 6/13 | ENST00000305202.9 | |
NECAB2 | NM_001329748.1 | c.497C>T | p.Thr166Ile | missense_variant | 6/12 | ||
NECAB2 | NM_001329749.2 | c.248C>T | p.Thr83Ile | missense_variant | 5/12 | ||
NECAB2 | XM_047434240.1 | c.248C>T | p.Thr83Ile | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECAB2 | ENST00000305202.9 | c.497C>T | p.Thr166Ile | missense_variant | 6/13 | 1 | NM_019065.3 | P1 | |
NECAB2 | ENST00000565691.5 | c.248C>T | p.Thr83Ile | missense_variant | 4/11 | 1 | |||
NECAB2 | ENST00000566836.1 | c.170C>T | p.Thr57Ile | missense_variant | 4/7 | 5 | |||
NECAB2 | ENST00000681513.1 | n.902C>T | non_coding_transcript_exon_variant | 6/13 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250376Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135378
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727244
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74438
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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 23, 2024 | The c.497C>T (p.T166I) alteration is located in exon 6 (coding exon 6) of the NECAB2 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the threonine (T) at amino acid position 166 to be replaced by an isoleucine (I). 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
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of ubiquitination at K171 (P = 0.1062);.;.;
MVP
ClinPred
D
GERP RS
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Splicing
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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