chr17-7317858-C-T

Variant names:

• chr17-7317858-C-T
• rs2072971554
• NM_032442.3:c.4135G>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.4135G>A​(p.Ala1379Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18
• 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=0.114259034).

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.4135G>A	p.Ala1379Thr	missense	Exon 26 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4129G>A	p.Ala1377Thr	missense	Exon 26 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.4135G>A	p.Ala1379Thr	missense	Exon 26 of 29	ENSP00000382390.2	Q96JN8-1
	NEURL4	ENST00000315614.11	TSL:1	c.4129G>A	p.Ala1377Thr	missense	Exon 26 of 29	ENSP00000319826.7	Q96JN8-2
	ENSG00000261915	ENST00000575474.1	TSL:5	n.574G>A		non_coding_transcript_exon	Exon 5 of 19	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

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	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
PhyloP100		3.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.080
Sift	Benign	0.47	T
Sift4G	Benign	0.43	T
Polyphen		0.035	B
Vest4		0.38
MutPred		0.13		Gain of phosphorylation at A1379 (P = 0.0098)
MVP		0.082
MPC		0.68
ClinPred		0.62	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.082
gMVP		0.63
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2072971554; hg19: chr17-7221177;