14-53043392-AGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1
The NM_001160148.2(DDHD1):c.*3370_*3375dupACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.25 ( 2662 hom., cov: 0)
Exomes 𝑓: 0.045 ( 0 hom. )
Consequence
DDHD1
NM_001160148.2 3_prime_UTR
NM_001160148.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.05
Publications
1 publications found
Genes affected
DDHD1 (HGNC:19714): (DDHD domain containing 1) This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
DDHD1 Gene-Disease associations (from GenCC):
- hereditary spastic paraplegiaInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hereditary spastic paraplegia 28Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001160148.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDHD1 | NM_001160148.2 | MANE Select | c.*3370_*3375dupACACAC | 3_prime_UTR | Exon 13 of 13 | NP_001153620.1 | Q8NEL9-1 | ||
| DDHD1 | NM_001160147.2 | c.*3370_*3375dupACACAC | 3_prime_UTR | Exon 13 of 13 | NP_001153619.1 | Q8NEL9-4 | |||
| DDHD1 | NM_030637.3 | c.*3370_*3375dupACACAC | 3_prime_UTR | Exon 12 of 12 | NP_085140.2 | Q8NEL9-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDHD1 | ENST00000673822.2 | MANE Select | c.*3370_*3375dupACACAC | 3_prime_UTR | Exon 13 of 13 | ENSP00000500986.2 | Q8NEL9-1 | ||
| DDHD1 | ENST00000395606.5 | TSL:2 | c.*3370_*3375dupACACAC | 3_prime_UTR | Exon 13 of 13 | ENSP00000378970.1 | Q8NEL9-4 | ||
| DDHD1 | ENST00000907173.1 | c.*3370_*3375dupACACAC | downstream_gene | N/A | ENSP00000577232.1 |
Frequencies
GnomAD3 genomes 0.247 AC: 27615AN: 111992Hom.: 2660 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
27615
AN:
111992
Hom.:
Cov.:
0
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:
GnomAD4 exome AF: 0.0455 AC: 1AN: 22Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1AN XY: 14 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
22
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
14
show subpopulations
African (AFR)
AF:
AC:
0
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
AC:
0
AN:
18
Other (OTH)
AF:
AC:
1
AN:
2
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.247 AC: 27633AN: 112078Hom.: 2662 Cov.: 0 AF XY: 0.250 AC XY: 13442AN XY: 53788 show subpopulations
GnomAD4 genome
AF:
AC:
27633
AN:
112078
Hom.:
Cov.:
0
AF XY:
AC XY:
13442
AN XY:
53788
show subpopulations
African (AFR)
AF:
AC:
9259
AN:
36208
American (AMR)
AF:
AC:
3521
AN:
11054
Ashkenazi Jewish (ASJ)
AF:
AC:
685
AN:
2760
East Asian (EAS)
AF:
AC:
1372
AN:
3548
South Asian (SAS)
AF:
AC:
828
AN:
2816
European-Finnish (FIN)
AF:
AC:
1187
AN:
5674
Middle Eastern (MID)
AF:
AC:
45
AN:
224
European-Non Finnish (NFE)
AF:
AC:
10148
AN:
47524
Other (OTH)
AF:
AC:
414
AN:
1566
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
926
1852
2778
3704
4630
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
282
564
846
1128
1410
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Hereditary spastic paraplegia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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