16-83978531-C-G

Variant names:

• chr16-83978531-C-G
• rs138901077
• NM_019065.3:c.314C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019065.3(NECAB2):​c.314C>G​(p.Thr105Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,461,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T105M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (1 hom.)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23577368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019065.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	NM_019065.3	MANE Select	c.314C>G	p.Thr105Arg	missense	Exon 3 of 13	NP_061938.2
	NECAB2	NM_001329748.1		c.314C>G	p.Thr105Arg	missense	Exon 3 of 12	NP_001316677.1
	NECAB2	NM_001329749.2		c.91C>G	p.Arg31Gly	missense	Exon 3 of 12	NP_001316678.1	Q7Z6G3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	ENST00000305202.9	TSL:1 MANE Select	c.314C>G	p.Thr105Arg	missense	Exon 3 of 13	ENSP00000307449.4	Q7Z6G3-1
	NECAB2	ENST00000565691.5	TSL:1	c.91C>G	p.Arg31Gly	missense	Exon 2 of 11	ENSP00000457354.1	Q7Z6G3-2
	NECAB2	ENST00000933975.1		c.314C>G	p.Thr105Arg	missense	Exon 3 of 13	ENSP00000604034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251418 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461568 Hom.: 1 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111776

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.24	T
PhyloP100		5.7
PROVEAN	Benign	-0.51	N
Sift	Benign	0.092	T
Sift4G	Benign	0.27	T
Vest4		0.32
MVP		0.32
ClinPred		0.85	D
GERP RS		4.8
PromoterAI		-0.047	Neutral
Varity_R		0.42
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs138901077; hg19: chr16-84012136;