Variant 6-24145929-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_080723.5(NRSN1):c.571C>G(p.Pro191Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000871 in 1,607,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NRSN1
NM_080723.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

Variant links:

Genes affected

NRSN1 (HGNC:17881): (neurensin 1) Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

NRSN1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRSN1	NM_080723.5 linkuse as main transcript	c.571C>G	p.Pro191Ala	missense_variant	4/4	ENST00000378491.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NRSN1	ENST00000378491.9 linkuse as main transcript	c.571C>G	p.Pro191Ala	missense_variant	4/4	1	NM_080723.5	P1
NRSN1	ENST00000378478.5 linkuse as main transcript	c.571C>G	p.Pro191Ala	missense_variant	4/4	1		P1
NRSN1	ENST00000468195.2 linkuse as main transcript	n.257-8842C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000286

AC:

AN:

244556

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132270

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1455292

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000162

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

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

Aug 10, 2021

The c.571C>G (p.P191A) alteration is located in exon 4 (coding exon 2) of the NRSN1 gene. This alteration results from a C to G substitution at nucleotide position 571, causing the proline (P) at amino acid position 191 to be replaced by an alanine (A). 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

0.29

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.26

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.47

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.76

MutPred

0.62

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.49

MPC

1.0

ClinPred

0.86

GERP RS

5.3

Varity_R

0.48

gMVP

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over