Variant 5-111730929-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004772.4(NREP):c.199T>C(p.Phe67Leu) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NREP
NM_004772.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.730

Variant links:

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]

NREP links:

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

STARD4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.085178286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NREP	NM_004772.4 linkuse as main transcript	c.199T>C	p.Phe67Leu	missense_variant	4/4	ENST00000257435.12	NP_004763.1
STARD4-AS1	NR_040093.1 linkuse as main transcript	n.1037-852A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NREP	ENST00000257435.12 linkuse as main transcript	c.199T>C	p.Phe67Leu	missense_variant	4/4	1	NM_004772.4	ENSP00000257435	P1	Q16612-1
STARD4-AS1	ENST00000500779.2 linkuse as main transcript	n.1037-852A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 04, 2022

The c.331T>C (p.F111L) alteration is located in exon 4 (coding exon 4) of the NREP gene. This alteration results from a T to C substitution at nucleotide position 331, causing the phenylalanine (F) at amino acid position 111 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;T;T;T;.;T;T;T;T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.48

.;.;T;.;T;.;.;.;.;.;.

M_CAP

Benign

0.0077

MetaRNN

Benign

0.085

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0040

B;B;B;B;.;B;B;B;B;B;B

Vest4

0.027

MutPred

0.28

Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);.;Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);Gain of catalytic residue at F67 (P = 0.0845);

MVP

0.18

MPC

0.23

ClinPred

0.69

GERP RS

1.4

Varity_R

0.046

gMVP

0.093

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over