Genetic Variant NM_001160148.2:c.*3372_*3375dupACAC (chr14-53043392-A-AGTGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

1 publications found

Variant links:

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

DDHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDHD1	NM_001160148.2	MANE Select	c.3372_3375dupACAC	3_prime_UTR	Exon 13 of 13	NP_001153620.1	Q8NEL9-1
DDHD1	NM_001160147.2		c.3372_3375dupACAC	3_prime_UTR	Exon 13 of 13	NP_001153619.1	Q8NEL9-4
DDHD1	NM_030637.3		c.3372_3375dupACAC	3_prime_UTR	Exon 12 of 12	NP_085140.2	Q8NEL9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDHD1	ENST00000673822.2	MANE Select	c.3372_3375dupACAC	3_prime_UTR	Exon 13 of 13	ENSP00000500986.2	Q8NEL9-1
DDHD1	ENST00000395606.5	TSL:2	c.3372_3375dupACAC	3_prime_UTR	Exon 13 of 13	ENSP00000378970.1	Q8NEL9-4
DDHD1	ENST00000907173.1		c.3372_3375dupACAC	downstream_gene	N/A	ENSP00000577232.1

Frequencies

GnomAD3 genomes

AF:

0.0903

AC:

10135

AN:

112264

Hom.:

818

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0904

AC:

10152

AN:

112350

Hom.:

817

Cov.:

AF XY:

0.0892

AC XY:

4815

AN XY:

53960

show subpopulations

African (AFR)

AF:

0.216

AC:

7838

AN:

36216

American (AMR)

AF:

0.0553

AC:

615

AN:

11118

Ashkenazi Jewish (ASJ)

AF:

0.0569

AC:

157

AN:

2760

East Asian (EAS)

AF:

0.00702

AC:

AN:

3562

South Asian (SAS)

AF:

0.0159

AC:

AN:

2828

European-Finnish (FIN)

AF:

0.0105

AC:

AN:

5714

Middle Eastern (MID)

AF:

0.0670

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0247

AC:

1178

AN:

47650

Other (OTH)

AF:

0.0738

AC:

116

AN:

1572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.00252

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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NM_001160148.2:c.3372_3375dupACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over