Variant 6-5999071-C-T 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_016588.3(NRN1):c.334G>A(p.Gly112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NRN1
NM_016588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

NRN1 (HGNC:17972): (neuritin 1) This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

NRN1 links:

NRN1 (HGNC:):

NRN1 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=0.09869638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRN1	NM_016588.3 linkuse as main transcript	c.334G>A	p.Gly112Ser	missense_variant	3/3	ENST00000244766.7	NP_057672.1	Q9NPD7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NRN1	ENST00000244766.7 linkuse as main transcript	c.334G>A	p.Gly112Ser	missense_variant	3/3	1	NM_016588.3	ENSP00000244766.2	Q9NPD7
NRN1	ENST00000622188.4 linkuse as main transcript	c.412G>A	p.Gly138Ser	missense_variant	4/4	2		ENSP00000480483.1	A0A087WWT2
NRN1	ENST00000616243.1 linkuse as main transcript	c.334G>A	p.Gly112Ser	missense_variant	4/4	4		ENSP00000484055.1	Q9NPD7
NRN1	ENST00000495850.1 linkuse as main transcript	n.417G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

May 27, 2022

The c.334G>A (p.G112S) alteration is located in exon 3 (coding exon 3) of the NRN1 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the glycine (G) at amino acid position 112 to be replaced by a serine (S). 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

Benign

0.063

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.065

T;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.060

N;.;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.090

N;.;.

REVEL

Benign

0.063

Sift

Benign

0.68

T;.;.

Sift4G

Benign

0.81

T;T;T

Polyphen

0.017

B;.;B

Vest4

0.31

MutPred

0.21

Gain of disorder (P = 0.0844);.;Gain of disorder (P = 0.0844);

MVP

0.043

MPC

0.71

ClinPred

0.73

GERP RS

2.6

Varity_R

0.054

gMVP

0.70

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