17-7317475-CCTCGGTCCAGCACT-C

Variant names:

• chr17-7317475-CCTCGGTCCAGCACT-C
• NM_032442.3:c.4290_4303delAGTGCTGGACCGAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032442.3(NEURL4):​c.4290_4303delAGTGCTGGACCGAG​(p.Val1431GlyfsTer99) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEURL4 NM_032442.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.10

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

Verdict is Uncertain_significance. Variant got 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.4290_4303delAGTGCTGGACCGAG	p.Val1431GlyfsTer99	frameshift_variant	Exon 27 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4284_4297delAGTGCTGGACCGAG	p.Val1429GlyfsTer99	frameshift_variant	Exon 27 of 29		NP_001005408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL4	ENST00000399464.7	c.4290_4303delAGTGCTGGACCGAG	p.Val1431GlyfsTer99	frameshift_variant	Exon 27 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.729_742delAGTGCTGGACCGAG		non_coding_transcript_exon_variant	Exon 6 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

NEURL4-related disorder Uncertain:1

Jan 03, 2022

3billion

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10% (PVS1_M). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7220794;