13-34942840-G-T

Position:

• chr13-34942840-G-T

Variant summary

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

The NM_001385012.1(NBEA):​c.20G>T​(p.Gly7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NBEA NM_001385012.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

Genes affected

NBEA (HGNC:7648): (neurobeachin) This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

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=0.078597695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.20G>T	p.Gly7Val	missense_variant	1/59	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.20G>T	p.Gly7Val	missense_variant	1/59	5	NM_001385012.1	ENSP00000369271.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.68
DEOGEN2	Benign	0.061	T;.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.040	N;N;.;N
REVEL	Benign	0.13
Sift	Benign	0.21	T;T;.;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.20
MutPred		0.17		Loss of glycosylation at P8 (P = 0.0648);Loss of glycosylation at P8 (P = 0.0648);Loss of glycosylation at P8 (P = 0.0648);Loss of glycosylation at P8 (P = 0.0648);
MVP		0.093
MPC		1.1
ClinPred		0.10	T
GERP RS		1.9
Varity_R		0.089
gMVP		0.62

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: chr13-35516977;