NM_017711.4:c.1231C>A

Variant names:

• chrX-70429987-C-A
• rs35552527
• NM_017711.4:c.1231C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017711.4(GDPD2):​c.1231C>A​(p.Arg411Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,207,215 control chromosomes in the GnomAD database, including 7 homozygotes. There are 228 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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. R411C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., 117 hem., cov: 23)
  • Exomes 𝑓: 0.00040 (3 hom. 111 hem.)
• Consequence: GDPD2 NM_017711.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 4 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]

ENSG00000284391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039965212).
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.1231C>A	p.Arg411Ser	missense	Exon 12 of 16	NP_060181.2
	GDPD2	NM_001171192.2		c.1231C>A	p.Arg411Ser	missense	Exon 12 of 17	NP_001164663.1	Q9HCC8-3
	GDPD2	NM_001171191.2		c.994C>A	p.Arg332Ser	missense	Exon 10 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.1231C>A	p.Arg411Ser	missense	Exon 12 of 16	ENSP00000363503.3	Q9HCC8-1
	GDPD2	ENST00000453994.6	TSL:2	c.1231C>A	p.Arg411Ser	missense	Exon 12 of 17	ENSP00000414019.2	Q9HCC8-3
	GDPD2	ENST00000913685.1		c.1231C>A	p.Arg411Ser	missense	Exon 12 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 453 AN: 112074 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00267

GnomAD2 exomes AF: 0.00124 AC: 227 AN: 183326 AF XY: 0.000885

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.000511

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000397 AC: 435 AN: 1095088 Hom.: 3 Cov.: 30 AF XY: 0.000308 AC XY: 111 AN XY: 360504

African (AFR) AF: 0.0139 AC: 367 AN: 26349

American (AMR) AF: 0.000597 AC: 21 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54055

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00000834 AC: 7 AN: 839265

Other (OTH) AF: 0.000869 AC: 40 AN: 46004

GnomAD4 genome AF: 0.00405 AC: 454 AN: 112127 Hom.: 4 Cov.: 23 AF XY: 0.00341 AC XY: 117 AN XY: 34301

African (AFR) AF: 0.0139 AC: 430 AN: 30872

American (AMR) AF: 0.00170 AC: 18 AN: 10609

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6125

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53238

Other (OTH) AF: 0.00264 AC: 4 AN: 1517

Alfa AF: 0.00102 Hom.: 54

Bravo AF: 0.00481

ESP6500AA AF: 0.0123 AC: 47

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00135 AC: 164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.78	N
PhyloP100		0.080
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.042
Sift	Benign	0.81	T
Sift4G	Benign	0.80	T
Polyphen		0.013	B
Vest4		0.22
MVP		0.34
MPC		0.49
ClinPred		0.0056	T
GERP RS		0.86
Varity_R		0.23
gMVP		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs35552527; hg19: chrX-69649837;