3-9943399-C-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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077415.3. 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
	CRELD1	NM_001077415.3	MANE Select	c.932C>A	p.Thr311Lys	missense	Exon 10 of 11	NP_001070883.2	Q96HD1-1
	CRELD1	NM_001374317.1		c.932C>A	p.Thr311Lys	missense	Exon 10 of 12	NP_001361246.1	A0A804HJJ0
	CRELD1	NM_001374318.1		c.932C>A	p.Thr311Lys	missense	Exon 9 of 11	NP_001361247.1	A0A804HJJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.932C>A	p.Thr311Lys	missense	Exon 10 of 11	ENSP00000393643.2	Q96HD1-1
	CRELD1	ENST00000326434.9	TSL:1	c.932C>A	p.Thr311Lys	missense	Exon 10 of 12	ENSP00000321856.5	Q96HD1-2
	CRELD1	ENST00000383811.8	TSL:1	c.932C>A	p.Thr311Lys	missense	Exon 9 of 10	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.72	N
PhyloP100		0.039
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.22
Sift	Benign	0.69	T
Sift4G	Benign	0.63	T
Polyphen		0.47	P
Vest4		0.44
MutPred		0.44		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;