3-9943412-G-C

Variant names:

• chr3-9943412-G-C
• rs76764016
• NM_001077415.3:c.945G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001077415.3(CRELD1):​c.945G>C​(p.Pro315Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P315P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRELD1 NM_001077415.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 9 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.

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.945G>C	p.Pro315Pro	synonymous	Exon 10 of 11	NP_001070883.2
	CRELD1	NM_001374317.1		c.945G>C	p.Pro315Pro	synonymous	Exon 10 of 12	NP_001361246.1
	CRELD1	NM_001374318.1		c.945G>C	p.Pro315Pro	synonymous	Exon 9 of 11	NP_001361247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.945G>C	p.Pro315Pro	synonymous	Exon 10 of 11	ENSP00000393643.2
	CRELD1	ENST00000326434.9	TSL:1	c.945G>C	p.Pro315Pro	synonymous	Exon 10 of 12	ENSP00000321856.5
	CRELD1	ENST00000383811.8	TSL:1	c.945G>C	p.Pro315Pro	synonymous	Exon 9 of 10	ENSP00000373322.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.018
DANN	Benign	0.80
PhyloP100		-3.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs76764016; hg19: chr3-9985096;