NM_001142651.3:c.524C>T

Variant names:

• chr5-172670277-C-T
• rs566946932
• NM_001142651.3:c.524C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001142651.3(NEURL1B):​c.524C>T​(p.Pro175Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,386,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786
• BS2: High AC in GnomAd4 at 6 AD gene.

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.524C>T	p.Pro175Leu	missense	Exon 2 of 5	NP_001136123.1	A8MQ27-1
	NEURL1B	NM_001308178.2		c.524C>T	p.Pro175Leu	missense	Exon 2 of 4	NP_001295107.1	A8MQ27-3
	NEURL1B	NM_001308177.2		c.32-13142C>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.524C>T	p.Pro175Leu	missense	Exon 2 of 5	ENSP00000358815.5	A8MQ27-1
	NEURL1B	ENST00000520919.5	TSL:1	c.524C>T	p.Pro175Leu	missense	Exon 2 of 4	ENSP00000429797.1	A8MQ27-3
	NEURL1B	ENST00000522853.5	TSL:1	c.32-13142C>T		intron	N/A	ENSP00000430001.1	A8MQ27-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000645 AC: 1 AN: 15504 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: 0.000145

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 176 AN: 1234200 Hom.: 0 Cov.: 31 AF XY: 0.000141 AC XY: 84 AN XY: 595700

African (AFR) AF: 0.0000417 AC: 1 AN: 23976

American (AMR) AF: 0.00 AC: 0 AN: 11898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17532

East Asian (EAS) AF: 0.00 AC: 0 AN: 28104

South Asian (SAS) AF: 0.00 AC: 0 AN: 56180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5100

European-Non Finnish (NFE) AF: 0.000170 AC: 171 AN: 1006940

Other (OTH) AF: 0.0000783 AC: 4 AN: 51090

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-9.5	D
REVEL	Uncertain	0.52
Sift	Benign	0.15	T
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MVP		0.73
MPC		1.4
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.73
gMVP		0.85
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs566946932; hg19: chr5-172097280;