Genetic Variant NM_013349.5:c.88C>T (chr1-212433031-C-T) – 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_013349.5(NENF):c.88C>T(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,181,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

NENF
NM_013349.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.16

Publications

0 publications found

Variant links:

Genes affected

NENF (HGNC:30384): (neudesin neurotrophic factor) This gene encodes a neurotrophic factor that may play a role in neuron differentiation and development. A pseudogene of this gene is found on chromosome 12. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2009]

NENF links:

ENSG00000287445 (HGNC:):

ENSG00000287445 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=0.10358092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013349.5. 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
	NENF	NM_013349.5	MANE Select	c.88C>T	p.Arg30Trp	missense	Exon 1 of 4	NP_037481.1	Q9UMX5
	NENF	NR_026598.2		n.112C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NENF	ENST00000366988.5	TSL:1 MANE Select	c.88C>T	p.Arg30Trp	missense	Exon 1 of 4	ENSP00000355955.3	Q9UMX5
NENF	ENST00000949005.1		c.88C>T	p.Arg30Trp	missense	Exon 1 of 4	ENSP00000619064.1
NENF	ENST00000949004.1		c.88C>T	p.Arg30Trp	missense	Exon 1 of 3	ENSP00000619063.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000621

AC:

AN:

1030798

Hom.:

Cov.:

AF XY:

0.0000473

AC XY:

AN XY:

485846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21040

American (AMR)

AF:

0.00

AC:

AN:

6732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12004

East Asian (EAS)

AF:

0.00

AC:

AN:

22074

South Asian (SAS)

AF:

0.00

AC:

AN:

19100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2640

European-Non Finnish (NFE)

AF:

0.0000709

AC:

AN:

888040

Other (OTH)

AF:

0.0000251

AC:

AN:

39870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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

AF:

0.0000132

AC:

AN:

151030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41312

American (AMR)

AF:

0.00

AC:

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67678

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.032

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-2.2

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.62

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Benign

0.083

Polyphen

0.0

Vest4

0.084

MutPred

0.36

Loss of methylation at R30 (P = 0.0055)

MVP

0.56

MPC

0.27

ClinPred

0.25

GERP RS

-6.7

PromoterAI

0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.52

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over