rs139717648

Positions:

• chr3-9944013-C-A
• chr3-9944013-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000326434.9(CRELD1):​c.1160C>A​(p.Thr387Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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. T387I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRELD1 ENST00000326434.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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]

(HGNC:):

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10776776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.1049-352C>A		intron_variant		ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.1049-352C>A		intron_variant		2	NM_001077415.3	ENSP00000393643	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.054
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.14	B
Vest4		0.18
MutPred		0.36		Gain of glycosylation at Y392 (P = 0.0146);
MVP		0.44
MPC		0.72
ClinPred		0.81	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.46

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

Other links and lift over

dbSNP: rs139717648; hg19: chr3-9985697;