5-172670234-G-A

Variant names:

• chr5-172670234-G-A
• rs1581431760
• NM_001142651.3:c.481G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142651.3(NEURL1B):​c.481G>A​(p.Gly161Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,259,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G161C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NEURL1B NM_001142651.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.12
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1470164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142651.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1B	NM_001142651.3	MANE Select	c.481G>A	p.Gly161Ser	missense	Exon 2 of 5	NP_001136123.1	A8MQ27-1
	NEURL1B	NM_001308178.2		c.481G>A	p.Gly161Ser	missense	Exon 2 of 4	NP_001295107.1	A8MQ27-3
	NEURL1B	NM_001308177.2		c.32-13185G>A		intron	N/A	NP_001295106.1	A8MQ27-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1B	ENST00000369800.6	TSL:1 MANE Select	c.481G>A	p.Gly161Ser	missense	Exon 2 of 5	ENSP00000358815.5	A8MQ27-1
	NEURL1B	ENST00000520919.5	TSL:1	c.481G>A	p.Gly161Ser	missense	Exon 2 of 4	ENSP00000429797.1	A8MQ27-3
	NEURL1B	ENST00000522853.5	TSL:1	c.32-13185G>A		intron	N/A	ENSP00000430001.1	A8MQ27-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1259682 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 611324

African (AFR) AF: 0.00 AC: 0 AN: 24878

American (AMR) AF: 0.00 AC: 0 AN: 15722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19222

East Asian (EAS) AF: 0.00 AC: 0 AN: 28636

South Asian (SAS) AF: 0.00 AC: 0 AN: 61110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1018562

Other (OTH) AF: 0.00 AC: 0 AN: 52304

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		8.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.090
Sift	Benign	1.0	T
Sift4G	Benign	0.65	T
Polyphen		0.43	B
Vest4		0.28
MutPred		0.43		Gain of glycosylation at G161 (P = 0.0315)
MVP		0.46
MPC		0.61
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.42
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs1581431760; hg19: chr5-172097237; COSMIC: COSV63939480;