5-172670255-T-A

Position:

• chr5-172670255-T-A

Variant summary

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

The NM_001142651.3(NEURL1B):​c.502T>A​(p.Cys168Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEURL1B NM_001142651.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEURL1B	NM_001142651.3	c.502T>A	p.Cys168Ser	missense_variant	2/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308178.2	c.502T>A	p.Cys168Ser	missense_variant	2/4		NP_001295107.1
NEURL1B	NM_001308177.2	c.32-13164T>A		intron_variant			NP_001295106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.502T>A	p.Cys168Ser	missense_variant	2/5	1	NM_001142651.3	ENSP00000358815.5
NEURL1B	ENST00000520919.5	c.502T>A	p.Cys168Ser	missense_variant	2/4	1		ENSP00000429797.1
NEURL1B	ENST00000522853.5	c.32-13164T>A		intron_variant		1		ENSP00000430001.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.502T>A (p.C168S) alteration is located in exon 2 (coding exon 2) of the NEURL1B gene. This alteration results from a T to A substitution at nucleotide position 502, causing the cysteine (C) at amino acid position 168 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.0043	.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.039
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.13	.;B
Vest4		0.69
MutPred		0.54		Gain of glycosylation at C168 (P = 0.0058);Gain of glycosylation at C168 (P = 0.0058);
MVP		0.62
MPC		0.66
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.17
gMVP		0.73

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: chr5-172097258;