17-7316155-G-T

Variant names:

• chr17-7316155-G-T
• rs761844941
• NM_032442.3:c.4657C>A

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.4657C>A​(p.Leu1553Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,430,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1553V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• 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=0.22767633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032442.3. 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
	NEURL4	NM_032442.3	MANE Select	c.4657C>A	p.Leu1553Ile	missense	Exon 29 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4651C>A	p.Leu1551Ile	missense	Exon 29 of 29	NP_001005408.1	Q96JN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL4	ENST00000399464.7	TSL:1 MANE Select	c.4657C>A	p.Leu1553Ile	missense	Exon 29 of 29	ENSP00000382390.2	Q96JN8-1
	NEURL4	ENST00000315614.11	TSL:1	c.4651C>A	p.Leu1551Ile	missense	Exon 29 of 29	ENSP00000319826.7	Q96JN8-2
	ENSG00000261915	ENST00000575474.1	TSL:5	n.975+121C>A		intron	N/A	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430794 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 713586

African (AFR) AF: 0.00 AC: 0 AN: 32892

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083628

Other (OTH) AF: 0.00 AC: 0 AN: 59320

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.074
Sift	Benign	0.31	T
Sift4G	Benign	0.33	T
Polyphen		0.50	P
Vest4		0.36
MutPred		0.22		Gain of catalytic residue at L1558 (P = 0.0733)
MVP		0.082
MPC		0.62
ClinPred		0.74	D
GERP RS		3.6
Varity_R		0.087
gMVP		0.11

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: rs761844941; hg19: chr17-7219474;