Variant 16-83968776-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019065.3(NECAB2):c.128A>C(p.Glu43Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 956,970 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.386

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]

NECAB2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033906102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NECAB2	NM_019065.3 linkuse as main transcript	c.128A>C	p.Glu43Ala	missense_variant	1/13	ENST00000305202.9
NECAB2	NM_001329748.1 linkuse as main transcript	c.128A>C	p.Glu43Ala	missense_variant	1/12
NECAB2	NM_001329749.2 linkuse as main transcript	c.-96A>C		5_prime_UTR_variant	1/12
NECAB2	XM_047434240.1 linkuse as main transcript	c.-22-3375A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECAB2	ENST00000305202.9 linkuse as main transcript	c.128A>C	p.Glu43Ala	missense_variant	1/13	1	NM_019065.3	P1	Q7Z6G3-1
NECAB2	ENST00000681513.1 linkuse as main transcript	n.533A>C		non_coding_transcript_exon_variant	1/13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000104

AC:

AN:

956970

Hom.:

Cov.:

AF XY:

0.00000222

AC XY:

AN XY:

449944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

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

Apr 07, 2023

The c.128A>C (p.E43A) alteration is located in exon 1 (coding exon 1) of the NECAB2 gene. This alteration results from a A to C substitution at nucleotide position 128, causing the glutamic acid (E) at amino acid position 43 to be replaced by an alanine (A). 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

0.060

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.33

M_CAP

Benign

0.0075

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.88

REVEL

Benign

0.064

Sift

Benign

0.41

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.058

MutPred

0.12

Loss of solvent accessibility (P = 0.0224);

MVP

0.014

ClinPred

0.17

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.051

gMVP

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over