rs140687246

Variant names:

• chr20-5547740-C-A
• rs140687246
• NM_019593.5:c.1940G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-5547740-C-A
• chr20-5547740-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019593.5(GPCPD1):​c.1940G>T​(p.Arg647Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R647C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPCPD1 NM_019593.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065310866).

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.1940G>T	p.Arg647Leu	missense	Exon 20 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.1940G>T	p.Arg647Leu	missense	Exon 20 of 20	ENSP00000368305.4	Q9NPB8
	GPCPD1	ENST00000718343.1		c.1940G>T	p.Arg647Leu	missense	Exon 20 of 20	ENSP00000520780.1	Q9NPB8
	GPCPD1	ENST00000873924.1		c.1940G>T	p.Arg647Leu	missense	Exon 21 of 21	ENSP00000543983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250916 AF XY: 0.00000738

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.32
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.075	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.47		Gain of sheet (P = 0.0085)
MVP		0.17
MPC		0.55
ClinPred		0.070	T
GERP RS		-2.1
Varity_R		0.076
gMVP		0.48
Mutation Taster		=89/11	polymorphism

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: rs140687246; hg19: chr20-5528386;