rs751953774
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001386795.1(DTNA):c.435G>A(p.Met145Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
DTNA
NM_001386795.1 missense
NM_001386795.1 missense
Scores
4
5
10
Clinical Significance
Conservation
PhyloP100: 6.76
Genes affected
DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.435G>A | p.Met145Ile | missense_variant | 5/23 | ENST00000444659.6 | NP_001373724.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.435G>A | p.Met145Ile | missense_variant | 5/23 | 5 | NM_001386795.1 | ENSP00000405819.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251162Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135736
GnomAD3 exomes
AF:
AC:
2
AN:
251162
Hom.:
AF XY:
AC XY:
1
AN XY:
135736
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727066
GnomAD4 exome
AF:
AC:
6
AN:
1461544
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
727066
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74268
GnomAD4 genome
AF:
AC:
1
AN:
152060
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74268
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
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 submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 04, 2015 | The p.Met145Ile variant in DTNA has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/65872 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 751953774). Computational prediction tools and conservation analysis do not prov ide strong support for or against an impact to the protein. In summary, the clin ical significance of the p.Met145Ile variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;.;.;.;.;.;.;.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;.;D;D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L;L;L;L;L;L;L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;N;N;.;.;.;N;.;N;N
REVEL
Benign
Sift
Benign
T;.;T;.;T;T;.;.;.;D;.;T;T
Sift4G
Uncertain
D;T;T;T;T;T;T;D;D;D;D;D;D
Polyphen
B;.;B;.;.;.;.;B;B;B;.;B;B
Vest4
MutPred
Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);Gain of ubiquitination at K143 (P = 0.1079);
MVP
MPC
0.37
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at