3-9940913-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001077415.3(CRELD1):​c.524G>C​(p.Arg175Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R175Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

CRELD1
NM_001077415.3 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.28
Variant links:
Genes affected
CRELD1 (HGNC:14630): (cysteine rich with EGF like domains 1) This gene encodes a member of a subfamily of epidermal growth factor-related proteins. The encoded protein is characterized by a cysteine-rich with epidermal growth factor-like domain. This protein may function as a cell adhesion molecule. Mutations in this gene are the cause of atrioventricular septal defect. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRELD1NM_001077415.3 linkuse as main transcriptc.524G>C p.Arg175Pro missense_variant 6/11 ENST00000452070.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRELD1ENST00000452070.6 linkuse as main transcriptc.524G>C p.Arg175Pro missense_variant 6/112 NM_001077415.3 P1Q96HD1-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T;T;T;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
.;.;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.81
D;D;D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Pathogenic
3.1
M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-6.5
D;D;D;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.013
D;D;D;D
Polyphen
0.54
P;P;P;P
Vest4
0.93
MutPred
0.25
Loss of glycosylation at S178 (P = 0.0693);Loss of glycosylation at S178 (P = 0.0693);Loss of glycosylation at S178 (P = 0.0693);Loss of glycosylation at S178 (P = 0.0693);
MVP
0.80
MPC
0.70
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.90
gMVP
0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759093681; hg19: chr3-9982597; API