chr16-83981077-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019065.3(NECAB2):ā€‹c.409C>Gā€‹(p.Leu137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.00015 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23858538).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECAB2NM_019065.3 linkuse as main transcriptc.409C>G p.Leu137Val missense_variant 5/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.409C>G p.Leu137Val missense_variant 5/12
NECAB2NM_001329749.2 linkuse as main transcriptc.160C>G p.Leu54Val missense_variant 4/12
NECAB2XM_047434240.1 linkuse as main transcriptc.160C>G p.Leu54Val missense_variant 4/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.409C>G p.Leu137Val missense_variant 5/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000565691.5 linkuse as main transcriptc.160C>G p.Leu54Val missense_variant 3/111 Q7Z6G3-2
NECAB2ENST00000566836.1 linkuse as main transcriptc.82C>G p.Leu28Val missense_variant 3/75
NECAB2ENST00000681513.1 linkuse as main transcriptn.814C>G non_coding_transcript_exon_variant 5/13

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251486
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000147
AC:
215
AN:
1461884
Hom.:
0
Cov.:
33
AF XY:
0.000133
AC XY:
97
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000181
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000161
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 GeneticsApr 07, 2022The c.409C>G (p.L137V) alteration is located in exon 5 (coding exon 5) of the NECAB2 gene. This alteration results from a C to G substitution at nucleotide position 409, causing the leucine (L) at amino acid position 137 to be replaced by a valine (V). 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
Uncertain
0.49
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T;.;T
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.19
FATHMM_MKL
Benign
0.54
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.24
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Pathogenic
3.1
M;.;.
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Benign
0.24
Sift
Benign
0.061
T;D;D
Sift4G
Uncertain
0.048
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.82
MVP
0.072
ClinPred
0.66
D
GERP RS
2.6
Varity_R
0.28
gMVP
0.54

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: rs150547119; hg19: chr16-84014682; API