NM_001077415.3:c.932C>A

Variant names:

• chr3-9943399-C-A
• rs28942092
• NM_001077415.3:c.932C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077415.3(CRELD1):​c.932C>A​(p.Thr311Lys) 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. 16/22 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. T311I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 0 publications found

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]

ENSG00000288550 (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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14414904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.932C>A	p.Thr311Lys	missense_variant	Exon 10 of 11	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.932C>A	p.Thr311Lys	missense_variant	Exon 10 of 11	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.*580C>A		non_coding_transcript_exon_variant	Exon 23 of 24			ENSP00000507040.1
ENSG00000288550	ENST00000683484.1	n.*580C>A		3_prime_UTR_variant	Exon 23 of 24			ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	0.0071	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T;T;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	.;.;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.72	N;N;N;N
PhyloP100		0.039
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.22	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.69	T;T;T;T
Sift4G	Benign	0.63	T;T;T;T
Polyphen		0.47	P;P;P;P
Vest4		0.44
MutPred		0.44		Gain of ubiquitination at T311 (P = 0.0031);Gain of ubiquitination at T311 (P = 0.0031);Gain of ubiquitination at T311 (P = 0.0031);Gain of ubiquitination at T311 (P = 0.0031);
MVP		0.90
MPC		0.26
ClinPred		0.42	T
GERP RS		1.9
Varity_R		0.051
gMVP		0.72
Mutation Taster		=15/85	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28942092; hg19: chr3-9985083;