10-103494424-C-T

Variant names:

• chr10-103494424-C-T
• rs776438581
• NM_004210.5:c.37C>T

Variant summary

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

The NM_004210.5(NEURL1):​c.37C>T​(p.Arg13*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NEURL1 NM_004210.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 0 publications found

Genes affected

NEURL1 (HGNC:7761): (neuralized E3 ubiquitin protein ligase 1) Predicted to enable translation factor activity, non-nucleic acid binding and ubiquitin protein ligase activity. Involved in negative regulation of Notch signaling pathway; negative regulation of cell population proliferation; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1-AS1 (HGNC:51220): (NEURL1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004210.5. 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
	NEURL1	NM_004210.5	MANE Select	c.37C>T	p.Arg13*	stop_gained	Exon 1 of 6	NP_004201.3
	NEURL1-AS1	NR_120675.1		n.294+137G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1	ENST00000369780.9	TSL:1 MANE Select	c.37C>T	p.Arg13*	stop_gained	Exon 1 of 6	ENSP00000358795.4	O76050-1
	NEURL1	ENST00000945279.1		c.37C>T	p.Arg13*	stop_gained	Exon 1 of 4	ENSP00000615338.1
	NEURL1-AS1	ENST00000453753.5	TSL:5	n.245+137G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446642 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718302

African (AFR) AF: 0.00 AC: 0 AN: 32946

American (AMR) AF: 0.00 AC: 0 AN: 43198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.00 AC: 0 AN: 38874

South Asian (SAS) AF: 0.00 AC: 0 AN: 84006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105264

Other (OTH) AF: 0.00 AC: 0 AN: 59730

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.39	N
PhyloP100		0.58
Vest4		0.24
GERP RS		2.6
Mutation Taster		=20/180	disease causing (fs/PTC)

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: rs776438581; hg19: chr10-105254181;