rs756454420

Variant names:

• chr17-7316209-G-A
• rs756454420
• NM_032442.3:c.4603C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7316209-G-A
• chr17-7316209-G-C

Variant summary

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

The NM_032442.3(NEURL4):​c.4603C>T​(p.Pro1535Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,646 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. P1535A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.19
• Publications: 0 publications found

Genes affected

NEURL4 (HGNC:34410): (neuralized E3 ubiquitin protein ligase 4) The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000261915 (HGNC:):

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=0.24494874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL4	NM_032442.3	c.4603C>T	p.Pro1535Ser	missense_variant	Exon 29 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4597C>T	p.Pro1533Ser	missense_variant	Exon 29 of 29		NP_001005408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL4	ENST00000399464.7	c.4603C>T	p.Pro1535Ser	missense_variant	Exon 29 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.975+67C>T		intron_variant	Intron 8 of 18	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459646 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726316

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60318

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	.;M;.
PhyloP100		8.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N;N;.
REVEL	Benign	0.17
Sift	Benign	0.21	T;T;.
Sift4G	Benign	0.27	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.18
MutPred		0.35		.;Gain of phosphorylation at P1535 (P = 0.0455);.;
MVP		0.27
MPC		0.55
ClinPred		0.95	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.46

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: rs756454420; hg19: chr17-7219528;