Genetic Variant GDPD1:p.Arg204Cys (chr17-59267074-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_182569.4(GDPD1):c.610C>T(p.Arg204Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,460,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GDPD1
NM_182569.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

Publications

2 publications found

Variant links:

Genes affected

GDPD1 (HGNC:20883): (glycerophosphodiester phosphodiesterase domain containing 1) This gene encodes a member of the glycerophosphodiester phosphodiesterase family of enzymes that catalyze the hydrolysis of deacylated glycerophospholipids to glycerol phosphate and alcohol. The encoded protein is localized to the cytoplasm and concentrates near the perinuclear region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

GDPD1 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

GDPD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

BS2

High AC in GnomAdExome4 at 40 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDPD1	NM_182569.4	MANE Select	c.610C>T	p.Arg204Cys	missense	Exon 7 of 10	NP_872375.2	Q8N9F7-1
GDPD1	NM_001165994.2		c.610C>T	p.Arg204Cys	missense	Exon 7 of 9	NP_001159466.1	Q8N9F7-2
GDPD1	NM_001165993.2		c.610C>T	p.Arg204Cys	missense	Exon 7 of 10	NP_001159465.1	Q8N9F7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDPD1	ENST00000284116.9	TSL:1 MANE Select	c.610C>T	p.Arg204Cys	missense	Exon 7 of 10	ENSP00000284116.4	Q8N9F7-1
GDPD1	ENST00000581276.5	TSL:1	c.610C>T	p.Arg204Cys	missense	Exon 7 of 9	ENSP00000464690.1	Q8N9F7-2
GDPD1	ENST00000581140.5	TSL:1	c.610C>T	p.Arg204Cys	missense	Exon 7 of 10	ENSP00000463273.1	Q8N9F7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251372

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1460372

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1110664

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

3.7

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.32

Sift

Benign

0.033

Sift4G

Uncertain

0.0050

Polyphen

0.94

Vest4

0.77

MutPred

0.72

Gain of sheet (P = 0.0827)

MVP

0.45

MPC

0.91

ClinPred

0.95

GERP RS

4.6

Varity_R

0.45

gMVP

0.82

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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