16-83981084-C-A

Position:

• chr16-83981084-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019065.3(NECAB2):​c.416C>A​(p.Thr139Asn) variant causes a missense change involving the alteration of a non-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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23242977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECAB2	NM_019065.3	c.416C>A	p.Thr139Asn	missense_variant	5/13	ENST00000305202.9
NECAB2	NM_001329748.1	c.416C>A	p.Thr139Asn	missense_variant	5/12
NECAB2	NM_001329749.2	c.167C>A	p.Thr56Asn	missense_variant	4/12
NECAB2	XM_047434240.1	c.167C>A	p.Thr56Asn	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECAB2	ENST00000305202.9	c.416C>A	p.Thr139Asn	missense_variant	5/13	1	NM_019065.3	P1
NECAB2	ENST00000565691.5	c.167C>A	p.Thr56Asn	missense_variant	3/11	1
NECAB2	ENST00000566836.1	c.89C>A	p.Thr30Asn	missense_variant	3/7	5
NECAB2	ENST00000681513.1	n.821C>A		non_coding_transcript_exon_variant	5/13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.50	N
LIST_S2	Uncertain	0.88	D;D;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.39
MutPred		0.18		Gain of relative solvent accessibility (P = 0.2363);.;.;
MVP		0.13
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.22
gMVP		0.49

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: chr16-84014689;