Variant chr14-53046752-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001160148.2(DDHD1):c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,436,872 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.022 ( 10 hom., cov: 30)

Exomes 𝑓: 0.00060 ( 11 hom. )

Consequence

DDHD1
NM_001160148.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.414

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-53046752-T-C is Benign according to our data. Variant chr14-53046752-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 382967.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDHD1	NM_001160148.2 linkuse as main transcript	c.*16A>G		3_prime_UTR_variant	13/13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2 linkuse as main transcript	c.*16A>G		3_prime_UTR_variant	13/13		NM_001160148.2	ENSP00000500986	A2	Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

907

AN:

41842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0793

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00650

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00194

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000928

Gnomad OTH

AF:

0.0137

GnomAD3 exomes

AF:

0.00386

AC:

332

AN:

85992

Hom.:

AF XY:

0.00255

AC XY:

120

AN XY:

47112

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000607

GnomAD4 exome

AF:

0.000601

AC:

838

AN:

1395030

Hom.:

Cov.:

AF XY:

0.000489

AC XY:

339

AN XY:

692598

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.0217

AC:

909

AN:

41842

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

430

AN XY:

19920

show subpopulations

Gnomad4 AFR

AF:

0.0793

Gnomad4 AMR

AF:

0.00650

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00196

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000928

Gnomad4 OTH

AF:

0.0135

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.00666

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over