5-172683443-C-A

Variant names:

• chr5-172683443-C-A
• rs1331448606
• NM_001142651.3:c.602C>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.602C>A​(p.Thr201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,295,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T201M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: NEURL1B NM_001142651.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• 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=0.10300496).

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.602C>A	p.Thr201Lys	missense	Exon 3 of 5	NP_001136123.1	A8MQ27-1
	NEURL1B	NM_001308177.2		c.56C>A	p.Thr19Lys	missense	Exon 2 of 4	NP_001295106.1	A8MQ27-2
	NEURL1B	NM_001308178.2		c.578-2728C>A		intron	N/A	NP_001295107.1	A8MQ27-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1B	ENST00000369800.6	TSL:1 MANE Select	c.602C>A	p.Thr201Lys	missense	Exon 3 of 5	ENSP00000358815.5	A8MQ27-1
	NEURL1B	ENST00000522853.5	TSL:1	c.56C>A	p.Thr19Lys	missense	Exon 2 of 4	ENSP00000430001.1	A8MQ27-2
	NEURL1B	ENST00000520919.5	TSL:1	c.578-2728C>A		intron	N/A	ENSP00000429797.1	A8MQ27-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1295682 Hom.: 0 Cov.: 30 AF XY: 0.00000157 AC XY: 1 AN XY: 636974

African (AFR) AF: 0.00 AC: 0 AN: 26270

American (AMR) AF: 0.00 AC: 0 AN: 23836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21062

East Asian (EAS) AF: 0.00 AC: 0 AN: 30598

South Asian (SAS) AF: 0.00 AC: 0 AN: 69384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5232

European-Non Finnish (NFE) AF: 9.67e-7 AC: 1 AN: 1033790

Other (OTH) AF: 0.0000187 AC: 1 AN: 53604

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.056
Sift	Benign	0.037	D
Sift4G	Benign	0.12	T
Polyphen		0.14	B
Vest4		0.33
MutPred		0.35		Gain of ubiquitination at T201 (P = 0.0155)
MVP		0.22
MPC		0.64
ClinPred		0.20	T
GERP RS		3.8
Varity_R		0.16
gMVP		0.55
Mutation Taster		=82/18	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: rs1331448606; hg19: chr5-172110446;