rs545506384

Variant names:

• chr10-103570988-C-G
• rs545506384
• NM_004210.5:c.202C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-103570988-C-G
• chr10-103570988-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004210.5(NEURL1):​c.202C>G​(p.His68Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H68Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEURL1 NM_004210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92

Genes affected

NEURL1 (HGNC:7761): (neuralized E3 ubiquitin protein ligase 1) Predicted to enable translation factor activity, non-nucleic acid binding and ubiquitin protein ligase activity. Involved in negative regulation of Notch signaling pathway; negative regulation of cell population proliferation; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42108744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL1	NM_004210.5	c.202C>G	p.His68Asp	missense_variant	Exon 2 of 6	ENST00000369780.9	NP_004201.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1	ENST00000369780.9	c.202C>G	p.His68Asp	missense_variant	Exon 2 of 6	1	NM_004210.5	ENSP00000358795.4
NEURL1	ENST00000437579.1	c.151C>G	p.His51Asp	missense_variant	Exon 2 of 3	2		ENSP00000416709.1
NEURL1	ENST00000455386	c.-24C>G		5_prime_UTR_variant	Exon 2 of 3	2		ENSP00000387714.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461740 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.23
Sift	Benign	0.23	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.32	B;.
Vest4		0.55
MutPred		0.48		Gain of catalytic residue at H68 (P = 0.0265);.;
MVP		0.42
MPC		1.2
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.43
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs545506384; hg19: chr10-105330745;