rs1026566263

Variant names:

• chr5-111731004-C-A
• rs1026566263
• NM_004772.4:c.124G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-111731004-C-A
• chr5-111731004-C-G
• chr5-111731004-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004772.4(NREP):​c.124G>T​(p.Asp42Tyr) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NREP NM_004772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418

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

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=0.14649051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NREP	NM_004772.4	c.124G>T	p.Asp42Tyr	missense_variant	Exon 4 of 4	ENST00000257435.12	NP_004763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NREP	ENST00000257435.12	c.124G>T	p.Asp42Tyr	missense_variant	Exon 4 of 4	1	NM_004772.4	ENSP00000257435.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T;T;T;T;.;T;T;T;T;T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	.;.;T;.;T;.;.;.;.;.;.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.0	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.044	D;D;D;D;D;D;D;D;D;D;D;.
Polyphen		0.92	P;P;P;P;.;P;P;P;P;P;P;D
Vest4		0.24
MutPred		0.14		Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);.;Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);Loss of ubiquitination at K39 (P = 0.0235);
MVP		0.76
MPC		0.81
ClinPred		0.63	D
GERP RS		2.1
Varity_R		0.14
gMVP		0.046

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

LitVar

Other links and lift over

dbSNP: rs1026566263; hg19: chr5-111066701;