dbSNP rs377470665: GDPD1:p.Leu254Ile (chr17-59270985-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_182569.4(GDPD1):c.760C>A(p.Leu254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. L254F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GDPD1
NM_182569.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36993918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD1	NM_182569.4 link	c.760C>A	p.Leu254Ile	missense_variant	Exon 8 of 10	ENST00000284116.9	NP_872375.2	Q8N9F7-1
GDPD1	NM_001165994.2 link	c.760C>A	p.Leu254Ile	missense_variant	Exon 8 of 9		NP_001159466.1	Q8N9F7-2
GDPD1	NM_001165993.2 link	c.760C>A	p.Leu254Ile	missense_variant	Exon 8 of 10		NP_001159465.1	Q8N9F7-3
GDPD1	XM_017024521.2 link	c.481C>A	p.Leu161Ile	missense_variant	Exon 5 of 7		XP_016880010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD1	ENST00000284116.9 link	c.760C>A	p.Leu254Ile	missense_variant	Exon 8 of 10	1	NM_182569.4	ENSP00000284116.4		Q8N9F7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715772

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32762

American (AMR)

AF:

0.00

AC:

AN:

43518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39126

South Asian (SAS)

AF:

0.00

AC:

AN:

83994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1092738

Other (OTH)

AF:

0.00

AC:

AN:

59418

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.033

T;.;.

Eigen

Benign

-0.094

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.0062

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

PhyloP100

2.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.54

N;.;.

REVEL

Benign

0.098

Sift

Benign

0.42

T;.;.

Sift4G

Benign

0.46

T;T;T

Polyphen

0.020

B;.;B

Vest4

0.50

MutPred

0.66

Gain of catalytic residue at L259 (P = 0.07);Gain of catalytic residue at L259 (P = 0.07);Gain of catalytic residue at L259 (P = 0.07);

MVP

0.43

MPC

0.59

ClinPred

0.70

GERP RS

4.7

Varity_R

0.24

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over