Genetic Variant GDPD4:p.Ile398TyrfsTer7 (chr11-77243743-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_182833.3(GDPD4):c.1191dupT(p.Ile398TyrfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,608,350 control chromosomes in the GnomAD database, including 97,675 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.27 ( 6339 hom., cov: 21)

Exomes 𝑓: 0.35 ( 91336 hom. )

Consequence

GDPD4
NM_182833.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150

Variant links:

Genes affected

GDPD4 (HGNC:24849): (glycerophosphodiester phosphodiesterase domain containing 4) Predicted to enable metal ion binding activity and phosphoric diester hydrolase activity. Predicted to be involved in lipid metabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GDPD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 11-77243743-T-TA is Benign according to our data. Variant chr11-77243743-T-TA is described in ClinVar as [Benign]. Clinvar id is 1277868.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3 link	c.1191dupT	p.Ile398TyrfsTer7	frameshift_variant	Exon 13 of 17	ENST00000315938.5	NP_878253.1	Q6W3E5-2
GDPD4	XM_011544834.1 link	c.1269dupT	p.Ile424TyrfsTer7	frameshift_variant	Exon 13 of 18		XP_011543136.1
GDPD4	XM_047426557.1 link	c.795+1537dupT		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1 link	c.795+1537dupT		intron_variant	Intron 10 of 12		XP_047282514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD4	ENST00000315938.5 link	c.1191dupT	p.Ile398TyrfsTer7	frameshift_variant	Exon 13 of 17	1	NM_182833.3	ENSP00000320815.4		Q6W3E5-2
GDPD4	ENST00000376217.6 link	c.1191dupT	p.Ile398TyrfsTer7	frameshift_variant	Exon 12 of 17	1		ENSP00000365390.2		Q6W3E5-1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40329

AN:

151934

Hom.:

6342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0965

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.307

AC:

77114

AN:

250800

Hom.:

13226

AF XY:

0.322

AC XY:

43636

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.0916

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.347

AC:

504816

AN:

1456298

Hom.:

91336

Cov.:

AF XY:

0.350

AC XY:

253357

AN XY:

724698

show subpopulations

Gnomad4 AFR exome

AF:

0.0861

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.265

AC:

40334

AN:

152052

Hom.:

6339

Cov.:

AF XY:

0.262

AC XY:

19508

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0966

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.311

Hom.:

1416

Bravo

AF:

0.254

Asia WGS

AF:

0.353

AC:

1228

AN:

3478

EpiCase

AF:

0.353

EpiControl

AF:

0.357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27421018) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -49

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