chr16-83990522-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019065.3(NECAB2):ā€‹c.488A>Gā€‹(p.Gln163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECAB2NM_019065.3 linkuse as main transcriptc.488A>G p.Gln163Arg missense_variant 6/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.488A>G p.Gln163Arg missense_variant 6/12
NECAB2NM_001329749.2 linkuse as main transcriptc.239A>G p.Gln80Arg missense_variant 5/12
NECAB2XM_047434240.1 linkuse as main transcriptc.239A>G p.Gln80Arg missense_variant 5/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.488A>G p.Gln163Arg missense_variant 6/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000565691.5 linkuse as main transcriptc.239A>G p.Gln80Arg missense_variant 4/111 Q7Z6G3-2
NECAB2ENST00000566836.1 linkuse as main transcriptc.161A>G p.Gln54Arg missense_variant 4/75
NECAB2ENST00000681513.1 linkuse as main transcriptn.893A>G non_coding_transcript_exon_variant 6/13

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000360
AC:
9
AN:
250326
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135344
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000489
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsSep 20, 2023The c.488A>G (p.Q163R) alteration is located in exon 6 (coding exon 6) of the NECAB2 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the glutamine (Q) at amino acid position 163 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;.;T
Eigen
Benign
0.18
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.068
D
MetaRNN
Uncertain
0.72
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.0
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.47
P;.;.
Vest4
0.83
MutPred
0.85
Gain of MoRF binding (P = 0.0134);.;.;
MVP
0.099
ClinPred
0.69
D
GERP RS
4.0
Varity_R
0.73
gMVP
0.66

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.

Other links and lift over

dbSNP: rs770058947; hg19: chr16-84024127; API