NEURL4 p.Thr1441Ser

Variant names:

• chr17-7317368-T-A
• NM_032442.3:c.4321A>T
• NEURL4 p.Thr1441Ser

Your query was ambiguous. Multiple possible variants found:

• chr17-7317368-T-A
• chr17-7317367-G-C
• chr17-7317366-AGT-GGA
• chr17-7317366-AGT-TGA
• chr17-7317366-AGT-CGA
• chr17-7317366-AG-GC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032442.3(NEURL4):​c.4321A>T​(p.Thr1441Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. T1441I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEURL4 NM_032442.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033201188).

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.4321A>T	p.Thr1441Ser	missense splice_region	Exon 28 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4315A>T	p.Thr1439Ser	missense splice_region	Exon 28 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.4321A>T	p.Thr1441Ser	missense splice_region	Exon 28 of 29	ENSP00000382390.2	Q96JN8-1
	NEURL4	ENST00000315614.11	TSL:1	c.4315A>T	p.Thr1439Ser	missense splice_region	Exon 28 of 29	ENSP00000319826.7	Q96JN8-2
	ENSG00000261915	ENST00000575474.1	TSL:5	n.760A>T		splice_region non_coding_transcript_exon	Exon 7 of 19	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.55
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.011
Sift	Benign	0.69	T
Sift4G	Benign	0.98	T
Varity_R		0.065
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-7220687;