rs767700057

Variant names:

• chrX-70426693-C-A
• rs767700057
• NM_017711.4:c.508C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-70426693-C-A
• chrX-70426693-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017711.4(GDPD2):​c.508C>A​(p.Leu170Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,095,938 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: GDPD2 NM_017711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.383
• Publications: 1 publications found

Genes affected

GDPD2 (HGNC:25974): (glycerophosphodiester phosphodiesterase domain containing 2) This gene encodes a member of the glycerophosphodiester phosphodiesterase enzyme family. The encoded protein hydrolyzes glycerophosphoinositol to produce inositol 1-phosphate and glycerol. This protein may have a role in osteoblast differentiation and growth. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07327369).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017711.4. 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
	GDPD2	NM_017711.4	MANE Select	c.508C>A	p.Leu170Ile	missense	Exon 7 of 16	NP_060181.2
	GDPD2	NM_001171192.2		c.508C>A	p.Leu170Ile	missense	Exon 7 of 17	NP_001164663.1	Q9HCC8-3
	GDPD2	NM_001171191.2		c.271C>A	p.Leu91Ile	missense	Exon 5 of 14	NP_001164662.1	Q9HCC8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDPD2	ENST00000374382.4	TSL:1 MANE Select	c.508C>A	p.Leu170Ile	missense	Exon 7 of 16	ENSP00000363503.3	Q9HCC8-1
	GDPD2	ENST00000453994.6	TSL:2	c.508C>A	p.Leu170Ile	missense	Exon 7 of 17	ENSP00000414019.2	Q9HCC8-3
	GDPD2	ENST00000913685.1		c.508C>A	p.Leu170Ile	missense	Exon 7 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180920 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000734

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: 0.00000182 AC: 2 AN: 1095938 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 361350

African (AFR) AF: 0.00 AC: 0 AN: 26382

American (AMR) AF: 0.0000569 AC: 2 AN: 35159

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30192

South Asian (SAS) AF: 0.00 AC: 0 AN: 53942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840263

Other (OTH) AF: 0.00 AC: 0 AN: 46024

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.38
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.032
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		0.0090	B
Vest4		0.27
MutPred		0.21		Gain of catalytic residue at L170 (P = 0.0486)
MVP		0.39
MPC		0.50
ClinPred		0.068	T
GERP RS		1.1
Varity_R		0.071
gMVP		0.48
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs767700057; hg19: chrX-69646543;