16-83968778-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_019065.3(NECAB2):ā€‹c.130T>Cā€‹(p.Ser44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NECAB2
NM_019065.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0290
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038244754).
BP6
Variant 16-83968778-T-C is Benign according to our data. Variant chr16-83968778-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534320.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECAB2NM_019065.3 linkuse as main transcriptc.130T>C p.Ser44Pro missense_variant 1/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.130T>C p.Ser44Pro missense_variant 1/12
NECAB2NM_001329749.2 linkuse as main transcriptc.-94T>C 5_prime_UTR_variant 1/12
NECAB2XM_047434240.1 linkuse as main transcriptc.-22-3373T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.130T>C p.Ser44Pro missense_variant 1/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000681513.1 linkuse as main transcriptn.535T>C non_coding_transcript_exon_variant 1/13

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
957888
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
450304
Gnomad4 AFR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.044
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
15
DANN
Benign
0.67
DEOGEN2
Benign
0.0067
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
0.26
N
REVEL
Benign
0.046
Sift
Benign
0.55
T
Sift4G
Benign
0.55
T
Polyphen
0.0
B
Vest4
0.050
MutPred
0.11
Loss of phosphorylation at S44 (P = 0.0075);
MVP
0.014
ClinPred
0.14
T
GERP RS
1.7
Varity_R
0.095
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84002383; API