20-5558757-T-C

Variant names:

• chr20-5558757-T-C
• rs1427379636
• NM_019593.5:c.1595A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019593.5(GPCPD1):​c.1595A>G​(p.Tyr532Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,445,664 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. Y532F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GPCPD1 NM_019593.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22
• Publications: 0 publications found

Genes affected

GPCPD1 (HGNC:26957): (glycerophosphocholine phosphodiesterase 1) Predicted to enable glycerophosphocholine phosphodiesterase activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within skeletal muscle tissue development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019593.5. 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
	GPCPD1	NM_019593.5	MANE Select	c.1595A>G	p.Tyr532Cys	missense	Exon 18 of 20	NP_062539.1	Q9NPB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPCPD1	ENST00000379019.7	TSL:1 MANE Select	c.1595A>G	p.Tyr532Cys	missense	Exon 18 of 20	ENSP00000368305.4	Q9NPB8
	GPCPD1	ENST00000718343.1		c.1595A>G	p.Tyr532Cys	missense	Exon 18 of 20	ENSP00000520780.1	Q9NPB8
	GPCPD1	ENST00000873924.1		c.1595A>G	p.Tyr532Cys	missense	Exon 19 of 21	ENSP00000543983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 243406 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1445664 Hom.: 0 Cov.: 26 AF XY: 0.00000278 AC XY: 2 AN XY: 720126

African (AFR) AF: 0.00 AC: 0 AN: 32750

American (AMR) AF: 0.00 AC: 0 AN: 42432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.00 AC: 0 AN: 84546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1102154

Other (OTH) AF: 0.00 AC: 0 AN: 59744

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.1	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.63		Gain of sheet (P = 0.0125)
MVP		0.44
MPC		1.5
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.86
gMVP		0.81
Mutation Taster		=14/86	disease causing

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: rs1427379636; hg19: chr20-5539403;