20-5557961-C-A

Variant names:

• chr20-5557961-C-A
• rs746067827
• NM_019593.5:c.1813G>T

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.1813G>T​(p.Gly605Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,433,898 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. G605R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GPCPD1 NM_019593.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• 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, 0.875

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.1813G>T	p.Gly605Cys	missense	Exon 19 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.1813G>T	p.Gly605Cys	missense	Exon 19 of 20	ENSP00000368305.4	Q9NPB8
	GPCPD1	ENST00000718343.1		c.1813G>T	p.Gly605Cys	missense	Exon 19 of 20	ENSP00000520780.1	Q9NPB8
	GPCPD1	ENST00000873924.1		c.1813G>T	p.Gly605Cys	missense	Exon 20 of 21	ENSP00000543983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433898 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 714814

African (AFR) AF: 0.00 AC: 0 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 43358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25754

East Asian (EAS) AF: 0.00 AC: 0 AN: 39324

South Asian (SAS) AF: 0.00 AC: 0 AN: 83780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090640

Other (OTH) AF: 0.00 AC: 0 AN: 59356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.027	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.72		Loss of helix (P = 3e-04)
MVP		0.42
MPC		1.4
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.93
Mutation Taster		=14/86	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs746067827; hg19: chr20-5538607;