NM_001093730.1:c.1445G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001093730.1(DYTN):​c.1445G>A​(p.Ser482Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DYTN
NM_001093730.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.954
Variant links:
Genes affected
DYTN (HGNC:23279): (dystrotelin) This gene belongs to the dystrophin superfamily, which is characterized by the presence of four EF-hand motifs and a ZZ-domain. It is a likely ortholog of the Drosophila 'discontinuous actin hexagon' gene. It is noteworthy that the coding region of this gene lacks two coding exons that are found in the mouse ortholog. Human transcripts including these two exons are subject to nonsense-mediated transcript decay (NMD). On the other hand, transcripts skipping the two coding exons are expressed at very low levels. While this gene maintains an intact CDS, it may be an evolving pseudogene. However, after a discussion about this gene within the RefSeq group, as well as in the consensus coding sequence (CCDS) collaboration, it was decided to keep it as a protein-coding gene in the RefSeq, Ensembl-GENCODE and the CCDS sets. [provided by RefSeq, Jul 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.049214363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYTNNM_001093730.1 linkc.1445G>A p.Ser482Asn missense_variant Exon 11 of 12 ENST00000452335.2 NP_001087199.1 A2CJ06

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYTNENST00000452335.2 linkc.1445G>A p.Ser482Asn missense_variant Exon 11 of 12 1 NM_001093730.1 ENSP00000396593.2 A2CJ06
DYTNENST00000674258.1 linkn.1996G>A non_coding_transcript_exon_variant Exon 14 of 15

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249018
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135092
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000223
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461674
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
Bravo
AF:
0.00000378
ExAC
AF:
0.0000331
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1445G>A (p.S482N) alteration is located in exon 11 (coding exon 11) of the DYTN gene. This alteration results from a G to A substitution at nucleotide position 1445, causing the serine (S) at amino acid position 482 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
0.093
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.34
DANN
Benign
0.78
DEOGEN2
Benign
0.0022
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.0080
Sift
Uncertain
0.021
D
Sift4G
Benign
0.43
T
Polyphen
0.012
B
Vest4
0.081
MutPred
0.15
Gain of helix (P = 0.0078);
MVP
0.014
MPC
0.026
ClinPred
0.029
T
GERP RS
-1.2
Varity_R
0.056
gMVP
0.093

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs79969810; hg19: chr2-207527815; API