3-9940976-G-T

Position:

• chr3-9940976-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001077415.3(CRELD1):​c.587G>T​(p.Gly196Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.68

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-9940976-G-T is Pathogenic according to our data. Variant chr3-9940976-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 2574124.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.587G>T	p.Gly196Val	missense_variant	6/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.587G>T	p.Gly196Val	missense_variant	6/11	2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ventricular septal defect 1 Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Cytogenetics- Mohapatra Lab, Banaras Hindu University

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0040	T;T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Uncertain	0.055	D
MutationAssessor	Benign	0.59	N;N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.75	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.57
MutPred		0.46		Loss of disorder (P = 0.0296);Loss of disorder (P = 0.0296);Loss of disorder (P = 0.0296);Loss of disorder (P = 0.0296);
MVP		0.96
MPC		0.42
ClinPred		0.62	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-9982660;