Genetic Variant NM_004772.4:c.55A>C (chr5-111735456-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004772.4(NREP):c.55A>C(p.Lys19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K19E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NREP
NM_004772.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271

Publications

0 publications found

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 was made for transcript

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=0.09567106).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NREP	NM_004772.4	MANE Select	c.55A>C	p.Lys19Gln	missense	Exon 3 of 4	NP_004763.1	Q16612-1
NREP	NM_001142475.2		c.187A>C	p.Lys63Gln	missense	Exon 3 of 4	NP_001135947.1	Q16612-2
NREP	NM_001142474.2		c.157A>C	p.Lys53Gln	missense	Exon 3 of 4	NP_001135946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NREP	ENST00000257435.12	TSL:1 MANE Select	c.55A>C	p.Lys19Gln	missense	Exon 3 of 4	ENSP00000257435.7	Q16612-1
NREP	ENST00000379671.7	TSL:1	c.55A>C	p.Lys19Gln	missense	Exon 4 of 5	ENSP00000368993.3	Q16612-1
NREP	ENST00000447165.6	TSL:1	c.55A>C	p.Lys19Gln	missense	Exon 2 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251136

AF XY:

0.00

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111082

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.15

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

PhyloP100

0.27

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.045

Sift

Benign

0.062

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.11

MutPred

0.18

Loss of methylation at K19 (P = 0.0036)

MVP

0.72

MPC

0.39

ClinPred

0.069

GERP RS

-2.0

Varity_R

0.078

gMVP

0.032

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over