rs1052951644

Variant names:

• chr14-53153080-C-G
• rs1052951644
• NM_001160148.2:c.19G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-53153080-C-G
• chr14-53153080-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001160148.2(DDHD1):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,293,154 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: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: DDHD1 NM_001160148.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.162
• Publications: 1 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23198414).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	NM_001160148.2	MANE Select	c.19G>C	p.Gly7Arg	missense	Exon 1 of 13	NP_001153620.1
	DDHD1	NM_001160147.2		c.19G>C	p.Gly7Arg	missense	Exon 1 of 13	NP_001153619.1
	DDHD1	NM_030637.3		c.19G>C	p.Gly7Arg	missense	Exon 1 of 12	NP_085140.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1293154 Hom.: 0 Cov.: 35 AF XY: 0.00000157 AC XY: 1 AN XY: 635288

African (AFR) AF: 0.00 AC: 0 AN: 25110

American (AMR) AF: 0.00 AC: 0 AN: 17600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20240

East Asian (EAS) AF: 0.0000338 AC: 1 AN: 29576

South Asian (SAS) AF: 0.00 AC: 0 AN: 65122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1043072

Other (OTH) AF: 0.00 AC: 0 AN: 53448

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.16
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.31
MutPred		0.14		Gain of MoRF binding (P = 0.0176)
MVP		0.082
MPC		0.97
ClinPred		0.70	D
GERP RS		3.7
PromoterAI		0.014	Neutral
Varity_R		0.18
gMVP		0.41
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1052951644; hg19: chr14-53619798;