rs752623474

Variant names:

• chr17-7316322-C-G
• rs752623474
• NM_032442.3:c.4490G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7316322-C-G
• chr17-7316322-C-T

Variant summary

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

The NM_032442.3(NEURL4):​c.4490G>C​(p.Arg1497Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R1497Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 2 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL4	NM_032442.3	c.4490G>C	p.Arg1497Pro	missense_variant	Exon 29 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4484G>C	p.Arg1495Pro	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.4490G>C	p.Arg1497Pro	missense_variant	Exon 29 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.929G>C		non_coding_transcript_exon_variant	Exon 8 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;L;.
PhyloP100		2.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.17	T;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.87	P;P;.
Vest4		0.64
MutPred		0.35		.;Loss of MoRF binding (P = 0.0048);.;
MVP		0.25
MPC		1.3
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.62
gMVP		0.80

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: rs752623474; hg19: chr17-7219641;