20-5558725-T-C

Variant names:

• chr20-5558725-T-C
• rs1179447177
• NM_019593.5:c.1627A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019593.5(GPCPD1):​c.1627A>G​(p.Thr543Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPCPD1 NM_019593.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPCPD1	NM_019593.5	c.1627A>G	p.Thr543Ala	missense_variant	Exon 18 of 20	ENST00000379019.7	NP_062539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPCPD1	ENST00000379019.7	c.1627A>G	p.Thr543Ala	missense_variant	Exon 18 of 20	1	NM_019593.5	ENSP00000368305.4
GPCPD1	ENST00000418646.5	c.400A>G	p.Thr134Ala	missense_variant	Exon 5 of 7	5		ENSP00000396720.1
GPCPD1	ENST00000481038.5	n.3035A>G		non_coding_transcript_exon_variant	Exon 13 of 15	2
GPCPD1	ENST00000633552.1	n.*470A>G		downstream_gene_variant		5		ENSP00000487616.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1448418 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 721172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.0000334

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1627A>G (p.T543A) alteration is located in exon 18 (coding exon 17) of the GPCPD1 gene. This alteration results from a A to G substitution at nucleotide position 1627, causing the threonine (T) at amino acid position 543 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Benign	0.29	T
Polyphen		0.78	P
Vest4		0.84
MutPred		0.51		Loss of glycosylation at T543 (P = 0.0321);
MVP		0.33
MPC		1.0
ClinPred		0.78	D
GERP RS		5.2
Varity_R		0.13
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs1179447177; hg19: chr20-5539371;