NREP p.Phe16Leu

Variant names:

• chr5-111735463-A-T
• NM_004772.4:c.48T>A
• NREP p.Phe16Leu

Your query was ambiguous. Multiple possible variants found:

• chr5-111735463-A-T
• chr5-111735463-A-C
• chr5-111735465-A-G
• chr5-111735463-AAA-GAG
• chr5-111735463-AAA-TAG
• chr5-111735463-AAA-CAG

Variant summary

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

The NM_004772.4(NREP):​c.48T>A​(p.Phe16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NREP NM_004772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

Genes affected

NREP (HGNC:16834): (neuronal regeneration related protein) Predicted to be involved in axon regeneration; regulation of neuron differentiation; and regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STARD4-AS1 (HGNC:44117): (STARD4 antisense RNA 1)

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_004772.4. 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
	NREP	NM_004772.4	MANE Select	c.48T>A	p.Phe16Leu	missense	Exon 3 of 4	NP_004763.1	Q16612-1
	NREP	NM_001142475.2		c.180T>A	p.Phe60Leu	missense	Exon 3 of 4	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.150T>A	p.Phe50Leu	missense	Exon 3 of 4	NP_001135946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NREP	ENST00000257435.12	TSL:1 MANE Select	c.48T>A	p.Phe16Leu	missense	Exon 3 of 4	ENSP00000257435.7	Q16612-1
	NREP	ENST00000379671.7	TSL:1	c.48T>A	p.Phe16Leu	missense	Exon 4 of 5	ENSP00000368993.3	Q16612-1
	NREP	ENST00000447165.6	TSL:1	c.48T>A	p.Phe16Leu	missense	Exon 2 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.29	T
PhyloP100		3.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.097
Mutation Taster		=76/24	polymorphism

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

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

Other links and lift over

hg19: chr5-111071160;