chr16-83990504-G-T

Variant names:

• chr16-83990504-G-T
• rs1043077031
• NM_019065.3:c.470G>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.470G>T​(p.Gly157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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=0.25126898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.470G>T	p.Gly157Val	missense_variant	Exon 6 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.470G>T	p.Gly157Val	missense_variant	Exon 6 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.221G>T	p.Gly74Val	missense_variant	Exon 5 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.221G>T	p.Gly74Val	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.470G>T	p.Gly157Val	missense_variant	Exon 6 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000565691.5	c.221G>T	p.Gly74Val	missense_variant	Exon 4 of 11	1		ENSP00000457354.1
NECAB2	ENST00000566836.1	c.143G>T	p.Gly48Val	missense_variant	Exon 4 of 7	5		ENSP00000455322.1
NECAB2	ENST00000681513.1	n.875G>T		non_coding_transcript_exon_variant	Exon 6 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249968 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135196

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T;.;T
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;N;D
REVEL	Benign	0.12
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.65	P;.;.
Vest4		0.48
MutPred		0.25		Loss of disorder (P = 0.0488);.;.;
MVP		0.18
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.23

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: rs1043077031; hg19: chr16-84024109;