chr16-83990531-C-A

Variant names:

• chr16-83990531-C-A
• rs763808340
• NM_019065.3:c.497C>A

Variant summary

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

The NM_019065.3(NECAB2):​c.497C>A​(p.Thr166Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78

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]

ACMG classification

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 rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.497C>A	p.Thr166Asn	missense_variant	Exon 6 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.497C>A	p.Thr166Asn	missense_variant	Exon 6 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.248C>A	p.Thr83Asn	missense_variant	Exon 5 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.248C>A	p.Thr83Asn	missense_variant	Exon 5 of 12		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.497C>A	p.Thr166Asn	missense_variant	Exon 6 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000565691.5	c.248C>A	p.Thr83Asn	missense_variant	Exon 4 of 11	1		ENSP00000457354.1
NECAB2	ENST00000566836.1	c.170C>A	p.Thr57Asn	missense_variant	Exon 4 of 7	5		ENSP00000455322.1
NECAB2	ENST00000681513.1	n.902C>A		non_coding_transcript_exon_variant	Exon 6 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250376 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135378

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: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727244

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: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.94
MutPred		0.70		Gain of helix (P = 0.0854);.;.;
MVP		0.28
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.77
gMVP		0.68

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

Other links and lift over

dbSNP: rs763808340; hg19: chr16-84024136;