chr13-34942922-T-G

Variant names:

• chr13-34942922-T-G
• rs767393352
• NM_001385012.1:c.102T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001385012.1(NBEA):​c.102T>G​(p.Gly34Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,922 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBEA NM_001385012.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.51
• Publications: 0 publications found

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]

NBEA Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without early-onset generalized epilepsy

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-34942922-T-G is Benign according to our data. Variant chr13-34942922-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2643739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385012.1. 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
	NBEA	NM_001385012.1	MANE Select	c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 59	NP_001371941.1	Q5T321
	NBEA	NM_001379245.1		c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 58	NP_001366174.1
	NBEA	NM_015678.5		c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 58	NP_056493.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	ENST00000379939.7	TSL:5 MANE Select	c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 59	ENSP00000369271.2	Q5T321
	NBEA	ENST00000400445.8	TSL:5	c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 58	ENSP00000383295.3	Q8NFP9-1
	NBEA	ENST00000691351.1		c.102T>G	p.Gly34Gly	synonymous	Exon 1 of 22	ENSP00000509284.1	A0A8I5QKR6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 134298 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367922 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 673160

African (AFR) AF: 0.00 AC: 0 AN: 29774

American (AMR) AF: 0.00 AC: 0 AN: 35954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22318

East Asian (EAS) AF: 0.00 AC: 0 AN: 34482

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062964

Other (OTH) AF: 0.00 AC: 0 AN: 56482

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 134380 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 65616

African (AFR) AF: 0.00 AC: 0 AN: 35518

American (AMR) AF: 0.00 AC: 0 AN: 13882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3194

East Asian (EAS) AF: 0.00 AC: 0 AN: 4616

South Asian (SAS) AF: 0.00 AC: 0 AN: 3864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61242

Other (OTH) AF: 0.00 AC: 0 AN: 1868

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.37
PhyloP100		-4.5

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: rs767393352; hg19: chr13-35517059;