rs757910491
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_032119.4(ADGRV1):c.968T>C(p.Ile323Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,880 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I323V) has been classified as Uncertain significance.
Frequency
Consequence
NM_032119.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.968T>C | p.Ile323Thr | missense_variant | 7/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.968T>C | p.Ile323Thr | missense_variant | 7/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000640281.1 | n.1027T>C | non_coding_transcript_exon_variant | 7/7 | 1 | ||||
ADGRV1 | ENST00000640083.1 | n.673T>C | non_coding_transcript_exon_variant | 5/6 | 5 | ||||
ADGRV1 | ENST00000640109.1 | n.1064T>C | non_coding_transcript_exon_variant | 7/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249108Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135132
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461646Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727096
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 24, 2018 | The p.Ile323Thr variant in ADGRV1 has not been previously reported in individual s with hearing loss, but has been identified in 2/24018 African chromosomes and 2/126614 European chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org; dbSNP rs757910491). Although this variant has been s een in the general population, its frequency is not high enough to rule out a pa thogenic role. Computational prediction tools and conservation analysis suggest that the p.Ile323Thr variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical si gnificance of the p.Ile323Thr variant is uncertain. ACMG/AMP Criteria applied: P M2; BP4. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at