14-53043392-AGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr14-53043392-A-AGTGT
• rs59747041
• NM_001160148.2:c.*3372_*3375dupACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001160148.2(DDHD1):​c.*3372_*3375dupACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.090 (817 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.*3372_*3375dupACAC		3_prime_UTR_variant	Exon 13 of 13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822	c.*3372_*3375dupACAC		3_prime_UTR_variant	Exon 13 of 13		NM_001160148.2	ENSP00000500986.2
DDHD1	ENST00000395606	c.*3372_*3375dupACAC		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000378970.1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 10135 AN: 112264 Hom.: 818 Cov.: 0

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0569

Gnomad EAS AF: 0.00701

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0672

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0741

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0904 AC: 10152 AN: 112350 Hom.: 817 Cov.: 0 AF XY: 0.0892 AC XY: 4815 AN XY: 53960

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0569

Gnomad4 EAS AF: 0.00702

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59747041; hg19: chr14-53510110;