5-172670241-C-T

Position:

• chr5-172670241-C-T

Variant summary

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

The NM_001142651.3(NEURL1B):​c.488C>T​(p.Pro163Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,251,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: NEURL1B NM_001142651.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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.488C>T	p.Pro163Leu	missense_variant	2/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308178.2	c.488C>T	p.Pro163Leu	missense_variant	2/4		NP_001295107.1
NEURL1B	NM_001308177.2	c.32-13178C>T		intron_variant			NP_001295106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.488C>T	p.Pro163Leu	missense_variant	2/5	1	NM_001142651.3	ENSP00000358815.5
NEURL1B	ENST00000520919.5	c.488C>T	p.Pro163Leu	missense_variant	2/4	1		ENSP00000429797.1
NEURL1B	ENST00000522853.5	c.32-13178C>T		intron_variant		1		ENSP00000430001.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1251906 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 606714

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.85e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.23
Sift	Benign	0.095	T;D
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	.;D
Vest4		0.53
MutPred		0.42		Gain of stability (P = 0.1068);Gain of stability (P = 0.1068);
MVP		0.45
MPC		1.3
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs1212661877; hg19: chr5-172097244;