rs926654530

Variant names:

• chr10-103571018-C-A
• NM_004210.5:c.232C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-103571018-C-A
• chr10-103571018-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004210.5(NEURL1):​c.232C>A​(p.Leu78Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L78V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEURL1 NM_004210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26667243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL1	NM_004210.5	c.232C>A	p.Leu78Ile	missense_variant	Exon 2 of 6	ENST00000369780.9	NP_004201.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1	ENST00000369780.9	c.232C>A	p.Leu78Ile	missense_variant	Exon 2 of 6	1	NM_004210.5	ENSP00000358795.4
NEURL1	ENST00000437579.1	c.181C>A	p.Leu61Ile	missense_variant	Exon 2 of 3	2		ENSP00000416709.1
NEURL1	ENST00000455386.1	c.7C>A	p.Leu3Ile	missense_variant	Exon 2 of 3	2		ENSP00000387714.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.91	P;.;.
Vest4		0.22
MutPred		0.46		Gain of catalytic residue at L78 (P = 0.0582);.;.;
MVP		0.24
MPC		0.88
ClinPred		0.74	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.11

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: chr10-105330775;