chr5-172670241-C-T

Variant names:

• chr5-172670241-C-T
• rs1212661877
• NM_001142651.3:c.488C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 2 ACMG points.

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

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.488C>T	p.Pro163Leu	missense	Exon 2 of 5	NP_001136123.1	A8MQ27-1
	NEURL1B	NM_001308178.2		c.488C>T	p.Pro163Leu	missense	Exon 2 of 4	NP_001295107.1	A8MQ27-3
	NEURL1B	NM_001308177.2		c.32-13178C>T		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.488C>T	p.Pro163Leu	missense	Exon 2 of 5	ENSP00000358815.5	A8MQ27-1
	NEURL1B	ENST00000520919.5	TSL:1	c.488C>T	p.Pro163Leu	missense	Exon 2 of 4	ENSP00000429797.1	A8MQ27-3
	NEURL1B	ENST00000522853.5	TSL:1	c.32-13178C>T		intron	N/A	ENSP00000430001.1	A8MQ27-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 25516 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 24650

American (AMR) AF: 0.00 AC: 0 AN: 14510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18720

East Asian (EAS) AF: 0.00 AC: 0 AN: 28384

South Asian (SAS) AF: 0.00 AC: 0 AN: 59660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5202

European-Non Finnish (NFE) AF: 9.85e-7 AC: 1 AN: 1014914

Other (OTH) AF: 0.00 AC: 0 AN: 51920

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.23
Sift	Benign	0.095	T
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.42		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
Mutation Taster		=21/79	disease causing

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: rs1212661877; hg19: chr5-172097244;