chr5-111731004-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 in silico tools predict 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. D42H) has been classified as Uncertain significance.

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14649051).

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.124G>T	p.Asp42Tyr	missense	Exon 4 of 4	NP_004763.1	Q16612-1
	NREP	NM_001142475.2		c.256G>T	p.Asp86Tyr	missense	Exon 4 of 4	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.226G>T	p.Asp76Tyr	missense	Exon 4 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.124G>T	p.Asp42Tyr	missense	Exon 4 of 4	ENSP00000257435.7	Q16612-1
	NREP	ENST00000379671.7	TSL:1	c.124G>T	p.Asp42Tyr	missense	Exon 5 of 5	ENSP00000368993.3	Q16612-1
	NREP	ENST00000447165.6	TSL:1	c.124G>T	p.Asp42Tyr	missense	Exon 3 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.42
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.044	D
Polyphen		0.92	P
Vest4		0.24
MutPred		0.14		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
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs1026566263; hg19: chr5-111066701;