11-77243755-C-T

Variant names:

• chr11-77243755-C-T
• NM_182833.3:c.1180G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_182833.3(GDPD4):​c.1180G>A​(p.Ala394Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GDPD4 NM_182833.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038615525).
• BP6: Variant 11-77243755-C-T is Benign according to our data. Variant chr11-77243755-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3519603.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD4	NM_182833.3	c.1180G>A	p.Ala394Thr	missense_variant	Exon 13 of 17	ENST00000315938.5	NP_878253.1
GDPD4	XM_011544834.1	c.1258G>A	p.Ala420Thr	missense_variant	Exon 13 of 18		XP_011543136.1
GDPD4	XM_047426557.1	c.795+1526G>A		intron_variant	Intron 10 of 12		XP_047282513.1
GDPD4	XM_047426558.1	c.795+1526G>A		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	c.1180G>A	p.Ala394Thr	missense_variant	Exon 13 of 17	1	NM_182833.3	ENSP00000320815.4
GDPD4	ENST00000376217.6	c.1180G>A	p.Ala394Thr	missense_variant	Exon 12 of 17	1		ENSP00000365390.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459520 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.012
DANN	Benign	0.73
DEOGEN2	Benign	0.00051	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.15	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.023
Sift	Benign	0.77	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0080	.;B
Vest4		0.026
MutPred		0.54		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.099
MPC		0.049
ClinPred		0.024	T
GERP RS		-4.3
Varity_R		0.028
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76954800;