rs10485741
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_000214.3(JAG1):c.744A>T(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P248P) has been classified as Benign.
Frequency
Consequence
NM_000214.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.744A>T | p.Pro248= | synonymous_variant | 5/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.744A>T | p.Pro248= | synonymous_variant | 5/26 | 1 | NM_000214.3 | P1 | |
JAG1 | ENST00000423891.6 | n.610A>T | non_coding_transcript_exon_variant | 3/25 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251246Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135806
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461146Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726918
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Tetralogy of Fallot Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Feb 02, 2022 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Alagille syndrome 1 (MIM#118450) and Tetralogy of Fallot (MIM#187500). The mechanism for Charcot-Marie-Tooth disease, axonal, type 2HH (MIM#619574) is not clearly established, but loss of function is suggested (PMID: 32065591). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0212 - Non-canonical splice region variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (2 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same position is present in gnomAD (v2) at a frequency of (18620 heterozygotes, 877 homozygotes). (I) 0505 - Abnormal splicing is predicted by in silico tools, with the loss of a donor site and retention of the canonical splice site. The affected nucleotide has low conservation. (I) 0709 - Another splice variant comparable to the one identified in this case has moderate previous evidence for being benign. This alternative nucleotide change (c.744A>G) has been reported many times as benign (ClinVar). (SB) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at