6-24145662-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080723.5(NRSN1):​c.304G>A​(p.Asp102Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,812 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: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NRSN1
NM_080723.5 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.85
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NRSN1NM_080723.5 linkuse as main transcriptc.304G>A p.Asp102Asn missense_variant 4/4 ENST00000378491.9 NP_542454.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NRSN1ENST00000378491.9 linkuse as main transcriptc.304G>A p.Asp102Asn missense_variant 4/41 NM_080723.5 ENSP00000367752 P1
NRSN1ENST00000378478.5 linkuse as main transcriptc.304G>A p.Asp102Asn missense_variant 4/41 ENSP00000367739 P1
NRSN1ENST00000378477.2 linkuse as main transcriptc.304G>A p.Asp102Asn missense_variant 4/41 ENSP00000367738
NRSN1ENST00000468195.2 linkuse as main transcriptn.257-9109G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251406
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135874
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 SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMay 14, 2024The c.304G>A (p.D102N) alteration is located in exon 4 (coding exon 2) of the NRSN1 gene. This alteration results from a G to A substitution at nucleotide position 304, causing the aspartic acid (D) at amino acid position 102 to be replaced by an asparagine (N). 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
0.34
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T;T;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.8
M;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.6
D;.;D
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D;.;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.91
MutPred
0.73
Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);
MVP
0.72
MPC
1.0
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.73
gMVP
0.80

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.

Other links and lift over

dbSNP: rs751622322; hg19: chr6-24145890; API