rs374832287

Variant names:

• chr17-7317344-G-A
• rs374832287
• NM_032442.3:c.4345C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7317344-G-A
• chr17-7317344-G-C
• chr17-7317344-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032442.3(NEURL4):​c.4345C>T​(p.Pro1449Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000499 in 1,401,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P1449A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26938105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL4	NM_032442.3	c.4345C>T	p.Pro1449Ser	missense_variant	Exon 28 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4339C>T	p.Pro1447Ser	missense_variant	Exon 28 of 29		NP_001005408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL4	ENST00000399464.7	c.4345C>T	p.Pro1449Ser	missense_variant	Exon 28 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.784C>T		non_coding_transcript_exon_variant	Exon 7 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000979 AC: 2 AN: 204328 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1401486 Hom.: 0 Cov.: 32 AF XY: 0.00000435 AC XY: 3 AN XY: 690222

African (AFR) AF: 0.00 AC: 0 AN: 31758

American (AMR) AF: 0.00 AC: 0 AN: 37206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.00 AC: 0 AN: 76880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1080268

Other (OTH) AF: 0.0000347 AC: 2 AN: 57692

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.011	.;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.1	.;L;.
PhyloP100		5.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.090	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.53	T;T;.
Sift4G	Benign	0.97	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.54
MutPred		0.23		.;Gain of phosphorylation at P1449 (P = 0.0331);.;
MVP		0.068
MPC		0.54
ClinPred		0.33	T
GERP RS		5.0
Varity_R		0.10
gMVP		0.54
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs374832287; hg19: chr17-7220663;