14-53043392-AGTGTGTGTGTGTGTGTGTGT-AGTGTGT

Variant names:

• chr14-53043392-AGTGTGTGTGTGTGT-A
• rs59747041
• NM_001160148.2:c.*3362_*3375delACACACACACACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001160148.2(DDHD1):​c.*3362_*3375delACACACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., cov: 0)
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 28

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*3362_*3375delACACACACACACAC		3_prime_UTR	Exon 13 of 13	NP_001153620.1	Q8NEL9-1
	DDHD1	NM_001160147.2		c.*3362_*3375delACACACACACACAC		3_prime_UTR	Exon 13 of 13	NP_001153619.1	Q8NEL9-4
	DDHD1	NM_030637.3		c.*3362_*3375delACACACACACACAC		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.*3362_*3375delACACACACACACAC		3_prime_UTR	Exon 13 of 13	ENSP00000500986.2	Q8NEL9-1
	DDHD1	ENST00000395606.5	TSL:2	c.*3362_*3375delACACACACACACAC		3_prime_UTR	Exon 13 of 13	ENSP00000378970.1	Q8NEL9-4
	DDHD1	ENST00000907173.1		c.*3362_*3375delACACACACACACAC		downstream_gene	N/A	ENSP00000577232.1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112418 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000351

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112418 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 53946

African (AFR) AF: 0.00 AC: 0 AN: 36234

American (AMR) AF: 0.00 AC: 0 AN: 11108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2762

East Asian (EAS) AF: 0.00 AC: 0 AN: 3566

South Asian (SAS) AF: 0.000351 AC: 1 AN: 2846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47682

Other (OTH) AF: 0.00 AC: 0 AN: 1554

Alfa AF: 0.00 Hom.: 108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59747041; hg19: chr14-53510110;