rs1758411673

Variant names:

• chr5-172683613-G-A
• rs1758411673
• NM_001142651.3:c.772G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-172683613-G-A
• chr5-172683613-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142651.3(NEURL1B):​c.772G>A​(p.Ala258Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,105,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. A258S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: NEURL1B NM_001142651.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10554108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL1B	NM_001142651.3	c.772G>A	p.Ala258Thr	missense_variant	Exon 3 of 5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2	c.226G>A	p.Ala76Thr	missense_variant	Exon 2 of 4		NP_001295106.1
NEURL1B	NM_001308178.2	c.578-2558G>A		intron_variant	Intron 2 of 3		NP_001295107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.772G>A	p.Ala258Thr	missense_variant	Exon 3 of 5	1	NM_001142651.3	ENSP00000358815.5
NEURL1B	ENST00000522853.5	c.226G>A	p.Ala76Thr	missense_variant	Exon 2 of 4	1		ENSP00000430001.1
NEURL1B	ENST00000520919.5	c.578-2558G>A		intron_variant	Intron 2 of 3	1		ENSP00000429797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000362 AC: 4 AN: 1105184 Hom.: 0 Cov.: 30 AF XY: 0.00000559 AC XY: 3 AN XY: 536440

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: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000215

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0022	.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.42	T;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.76	.;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.065
Sift	Benign	0.55	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.089	.;B
Vest4		0.069
MutPred		0.25		.;Gain of glycosylation at A258 (P = 0.0053);
MVP		0.14
MPC		0.50
ClinPred		0.33	T
GERP RS		3.6
Varity_R		0.074
gMVP		0.35

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: rs1758411673; hg19: chr5-172110616;