NM_001378026.1:c.263C>T

Variant names:

• chr2-203049933-C-T
• rs1368439283
• NM_001378026.1:c.263C>T

Variant summary

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

The NM_001378026.1(NBEAL1):​c.263C>T​(p.Ala88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,402,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NBEAL1 NM_001378026.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

NBEAL1 (HGNC:20681): (neurobeachin like 1) Predicted to enable protein kinase binding activity. Predicted to be involved in protein localization. Predicted to be active in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17084774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378026.1. 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
	NBEAL1	NM_001378026.1	MANE Select	c.263C>T	p.Ala88Val	missense	Exon 4 of 56	NP_001364955.1	A0A804HKS6
	NBEAL1	NM_001114132.2		c.263C>T	p.Ala88Val	missense	Exon 4 of 55	NP_001107604.1	Q6ZS30-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL1	ENST00000683969.1	MANE Select	c.263C>T	p.Ala88Val	missense	Exon 4 of 56	ENSP00000508055.1	A0A804HKS6
	NBEAL1	ENST00000478884.5	TSL:1	n.550C>T		non_coding_transcript_exon	Exon 4 of 7
	NBEAL1	ENST00000449802.5	TSL:5	c.263C>T	p.Ala88Val	missense	Exon 4 of 55	ENSP00000399903.1	Q6ZS30-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1402702 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691858

African (AFR) AF: 0.00 AC: 0 AN: 32268

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 37008

South Asian (SAS) AF: 0.00 AC: 0 AN: 79574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1079688

Other (OTH) AF: 0.00 AC: 0 AN: 58146

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0038	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.069
Sift	Benign	0.25	T
Sift4G	Benign	0.093	T
Polyphen		0.54	P
Vest4		0.26
MutPred		0.29		Loss of disorder (P = 0.0768)
MVP		0.64
MPC		0.12
ClinPred		0.53	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.18
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1368439283; hg19: chr2-203914656;