rs138901077

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-83978531-C-G
• chr16-83978531-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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=0.23577368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.314C>G	p.Thr105Arg	missense_variant	Exon 3 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.314C>G	p.Thr105Arg	missense_variant	Exon 3 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.91C>G	p.Arg31Gly	missense_variant	Exon 3 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.91C>G	p.Arg31Gly	missense_variant	Exon 3 of 12		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.314C>G	p.Thr105Arg	missense_variant	Exon 3 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000565691.5	c.91C>G	p.Arg31Gly	missense_variant	Exon 2 of 11	1		ENSP00000457354.1
NECAB2	ENST00000681513.1	n.719C>G		non_coding_transcript_exon_variant	Exon 3 of 13
NECAB2	ENST00000566836.1	c.-14C>G		upstream_gene_variant		5		ENSP00000455322.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251418 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135884

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: 0.0000176

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

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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: rs138901077; hg19: chr16-84012136;