7-37920952-G-C

Variant names:

• chr7-37920952-G-C
• NM_017549.5:c.13G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017549.5(EPDR1):​c.13G>C​(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,226 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. A5S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EPDR1 NM_017549.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39805037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPDR1	NM_017549.5	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 3	ENST00000199448.9	NP_060019.2
EPDR1	NM_001242946.2	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 2		NP_001229875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPDR1	ENST00000199448.9	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 3	1	NM_017549.5	ENSP00000199448.4
EPDR1	ENST00000423717.1	c.13G>C	p.Ala5Pro	missense_variant	Exon 1 of 2	1		ENSP00000409211.1
ENSG00000290149	ENST00000476620.1	c.-37-27888G>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1
SFRP4	ENST00000447200.2	c.43+5728C>G		intron_variant	Intron 2 of 5	5		ENSP00000402262.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446226 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718340

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0070	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.66	T;T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.038	D;D
Vest4		0.43
MVP		0.16
MPC		0.22
ClinPred		0.31	T
GERP RS		2.5
Varity_R		0.15
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-37960554;