NM_017549.5:c.362C>G

Variant names:

• chr7-37948932-C-G
• rs149095633
• NM_017549.5:c.362C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017549.5(EPDR1):​c.362C>G​(p.Pro121Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000743 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P121L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: EPDR1 NM_017549.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94
• Publications: 3 publications found

Genes affected

EPDR1 (HGNC:17572): (ependymin related 1) The protein encoded by this gene is a type II transmembrane protein that is similar to two families of cell adhesion molecules, the protocadherins and ependymins. This protein may play a role in calcium-dependent cell adhesion. This protein is glycosylated, and the orthologous mouse protein is localized to the lysosome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 8. [provided by RefSeq, Aug 2011]

ENSG00000290149 (HGNC:):

SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

SFRP4 Gene-Disease associations (from GenCC):

• Pyle disease

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08986384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017549.5. 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
	EPDR1	NM_017549.5	MANE Select	c.362C>G	p.Pro121Arg	missense	Exon 2 of 3	NP_060019.2	Q9UM22-1
	EPDR1	NM_001242948.2		c.179C>G	p.Pro60Arg	missense	Exon 2 of 3	NP_001229877.1	Q9UM22-3
	EPDR1	NM_001242946.2		c.270-1268C>G		intron	N/A	NP_001229875.2	Q9UM22-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPDR1	ENST00000199448.9	TSL:1 MANE Select	c.362C>G	p.Pro121Arg	missense	Exon 2 of 3	ENSP00000199448.4	Q9UM22-1
	EPDR1	ENST00000425345.1	TSL:1	c.179C>G	p.Pro60Arg	missense	Exon 2 of 3	ENSP00000413359.1	Q9UM22-3
	ENSG00000290149	ENST00000476620.1	TSL:4	c.56C>G	p.Pro19Arg	missense	Exon 3 of 4	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251388 AF XY: 0.000169

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000609 AC: 89 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.0000591 AC XY: 43 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000961 AC: 43 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1112002

Other (OTH) AF: 0.000248 AC: 15 AN: 60396

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74384

African (AFR) AF: 0.0000482 AC: 2 AN: 41496

American (AMR) AF: 0.00164 AC: 25 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00000732 Hom.: 0

Bravo AF: 0.000268

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.9
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.017	D
Vest4		0.34
MVP		0.24
MPC		0.27
ClinPred		0.16	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.36
Mutation Taster		=83/17	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: rs149095633; hg19: chr7-37988534;