5-172669842-A-C

Position:

• chr5-172669842-A-C

Variant summary

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

The NM_001142651.3(NEURL1B):​c.89A>C​(p.Glu30Ala) 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. 13/20 in silico tools predict a benign outcome for this variant. 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: 3.48

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=0.17497769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEURL1B	NM_001142651.3	c.89A>C	p.Glu30Ala	missense_variant	2/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308178.2	c.89A>C	p.Glu30Ala	missense_variant	2/4		NP_001295107.1
NEURL1B	NM_001308177.2	c.32-13577A>C		intron_variant			NP_001295106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.89A>C	p.Glu30Ala	missense_variant	2/5	1	NM_001142651.3	ENSP00000358815.5
NEURL1B	ENST00000520919.5	c.89A>C	p.Glu30Ala	missense_variant	2/4	1		ENSP00000429797.1
NEURL1B	ENST00000522853.5	c.32-13577A>C		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

Dec 03, 2021

The c.89A>C (p.E30A) alteration is located in exon 2 (coding exon 2) of the NEURL1B gene. This alteration results from a A to C substitution at nucleotide position 89, causing the glutamic acid (E) at amino acid position 30 to be replaced by an alanine (A). 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	Benign	0.17
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.012
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.10
Sift	Benign	0.16	T;D
Sift4G	Benign	0.68	T;T
Polyphen		0.018	.;B
Vest4		0.19
MutPred		0.10		Gain of methylation at R32 (P = 0.0752);Gain of methylation at R32 (P = 0.0752);
MVP		0.57
MPC		0.63
ClinPred		0.47	T
GERP RS		5.5
Varity_R		0.12
gMVP		0.58

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: chr5-172096845;