Variant rs770058947 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_019065.3(NECAB2):c.488A>C(p.Gln163Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

NECAB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3 link	c.488A>C	p.Gln163Pro	missense_variant	Exon 6 of 13	ENST00000305202.9	NP_061938.2	Q7Z6G3-1
NECAB2	NM_001329748.1 link	c.488A>C	p.Gln163Pro	missense_variant	Exon 6 of 12		NP_001316677.1
NECAB2	NM_001329749.2 link	c.239A>C	p.Gln80Pro	missense_variant	Exon 5 of 12		NP_001316678.1	Q7Z6G3-2
NECAB2	XM_047434240.1 link	c.239A>C	p.Gln80Pro	missense_variant	Exon 5 of 12		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NECAB2	ENST00000305202.9 link	c.488A>C	p.Gln163Pro	missense_variant	Exon 6 of 13	1	NM_019065.3	ENSP00000307449.4	Q7Z6G3-1
NECAB2	ENST00000565691.5 link	c.239A>C	p.Gln80Pro	missense_variant	Exon 4 of 11	1		ENSP00000457354.1	Q7Z6G3-2
NECAB2	ENST00000566836.1 link	c.161A>C	p.Gln54Pro	missense_variant	Exon 4 of 7	5		ENSP00000455322.1	H3BPH6
NECAB2	ENST00000681513.1 link	n.893A>C		non_coding_transcript_exon_variant	Exon 6 of 13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250326

Hom.:

AF XY:

0.00000739

AC XY:

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:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.95

MutPred

0.82

Loss of helix (P = 0.0626);.;.;

MVP

0.21

ClinPred

0.98

GERP RS

4.0

Varity_R

0.90

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over