chr14-53153080-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001160148.2(DDHD1):c.19G>A(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,445,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

DDHD1
NM_001160148.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.162

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 links:

DDHD1-DT (HGNC:55441): (DDHD1 divergent transcript)

DDHD1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18323657).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
DDHD1	NM_001160148.2	MANE Select	c.19G>A	p.Gly7Arg	missense	Exon 1 of 13	NP_001153620.1	Q8NEL9-1
DDHD1	NM_001160147.2		c.19G>A	p.Gly7Arg	missense	Exon 1 of 13	NP_001153619.1	Q8NEL9-4
DDHD1	NM_030637.3		c.19G>A	p.Gly7Arg	missense	Exon 1 of 12	NP_085140.2	Q8NEL9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDHD1	ENST00000673822.2	MANE Select	c.19G>A	p.Gly7Arg	missense	Exon 1 of 13	ENSP00000500986.2	Q8NEL9-1
DDHD1	ENST00000357758.3	TSL:1	c.19G>A	p.Gly7Arg	missense	Exon 1 of 12	ENSP00000350401.3	Q8NEL9-2
DDHD1	ENST00000907176.1		c.19G>A	p.Gly7Arg	missense	Exon 1 of 15	ENSP00000577235.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000715

AC:

AN:

41958

AF XY:

0.000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000464

AC:

AN:

1293154

Hom.:

Cov.:

AF XY:

0.00000630

AC XY:

AN XY:

635288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25110

American (AMR)

AF:

0.000284

AC:

AN:

17600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20240

East Asian (EAS)

AF:

0.00

AC:

AN:

29576

South Asian (SAS)

AF:

0.00

AC:

AN:

65122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043072

Other (OTH)

AF:

0.0000187

AC:

AN:

53448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41384

American (AMR)

AF:

0.000131

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67920

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary spastic paraplegia 28 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0068

Eigen

Benign

0.048

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.16

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.51

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.31

MutPred

0.14

Gain of MoRF binding (P = 0.0176)

MVP

0.093

MPC

0.97

ClinPred

0.26

GERP RS

3.7

PromoterAI

0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.18

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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