17-7317253-G-A

Variant names:

• chr17-7317253-G-A
• rs1238820739
• NM_032442.3:c.4436C>T

Variant summary

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

The NM_032442.3(NEURL4):​c.4436C>T​(p.Ser1479Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S1479C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• 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 2 ACMG points.

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

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.4436C>T	p.Ser1479Phe	missense	Exon 28 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4430C>T	p.Ser1477Phe	missense	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.4436C>T	p.Ser1479Phe	missense	Exon 28 of 29	ENSP00000382390.2	Q96JN8-1
	NEURL4	ENST00000315614.11	TSL:1	c.4430C>T	p.Ser1477Phe	missense	Exon 28 of 29	ENSP00000319826.7	Q96JN8-2
	ENSG00000261915	ENST00000575474.1	TSL:5	n.875C>T		non_coding_transcript_exon	Exon 7 of 19	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371000 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 672992

African (AFR) AF: 0.00 AC: 0 AN: 30402

American (AMR) AF: 0.00 AC: 0 AN: 29568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20234

East Asian (EAS) AF: 0.00 AC: 0 AN: 38544

South Asian (SAS) AF: 0.00 AC: 0 AN: 71006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069352

Other (OTH) AF: 0.00 AC: 0 AN: 56352

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.015	D
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.87
MutPred		0.19		Loss of phosphorylation at S1479 (P = 0.0407)
MVP		0.24
MPC		0.62
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.44
gMVP		0.90

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: rs1238820739; hg19: chr17-7220572;