Variant 6-24145653-G-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_080723.5(NRSN1):c.295G>T(p.Val99Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NRSN1
NM_080723.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10478401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRSN1	NM_080723.5 linkuse as main transcript	c.295G>T	p.Val99Leu	missense_variant	4/4	ENST00000378491.9	NP_542454.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NRSN1	ENST00000378491.9 linkuse as main transcript	c.295G>T	p.Val99Leu	missense_variant	4/4	1	NM_080723.5	ENSP00000367752	P1
NRSN1	ENST00000378478.5 linkuse as main transcript	c.295G>T	p.Val99Leu	missense_variant	4/4	1		ENSP00000367739	P1
NRSN1	ENST00000378477.2 linkuse as main transcript	c.295G>T	p.Val99Leu	missense_variant	4/4	1		ENSP00000367738
NRSN1	ENST00000468195.2 linkuse as main transcript	n.257-9118G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Jul 21, 2021

The c.295G>T (p.V99L) alteration is located in exon 4 (coding exon 2) of the NRSN1 gene. This alteration results from a G to T substitution at nucleotide position 295, causing the valine (V) at amino acid position 99 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.012

T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.15

N;N;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

0.23

N;.;N

REVEL

Benign

0.040

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.93

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.13

MutPred

0.27

Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);

MVP

0.53

MPC

0.29

ClinPred

0.040

GERP RS

2.6

Varity_R

0.029

gMVP

0.49

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