14-53043392-AGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr14-53043392-A-AGT
• rs59747041
• NM_001160148.2:c.*3374_*3375dupAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001160148.2(DDHD1):​c.*3374_*3375dupAC 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 0.028 (31 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0276 (3104/112452) while in subpopulation AFR AF= 0.0345 (1253/36306). AF 95% confidence interval is 0.0329. There are 31 homozygotes in gnomad4. There are 1527 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.*3374_*3375dupAC		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.*3374_*3375dupAC		3_prime_UTR_variant	Exon 13 of 13		NM_001160148.2	ENSP00000500986.2
DDHD1	ENST00000395606	c.*3374_*3375dupAC		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000378970.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 3102 AN: 112364 Hom.: 33 Cov.: 0

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0232

Gnomad EAS AF: 0.00393

Gnomad SAS AF: 0.00949

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0245

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: 0.0276 AC: 3104 AN: 112452 Hom.: 31 Cov.: 0 AF XY: 0.0283 AC XY: 1527 AN XY: 54008

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.0232

Gnomad4 EAS AF: 0.00393

Gnomad4 SAS AF: 0.00883

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0254

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;