4-22387745-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000334304.10(ADGRA3):āc.3926A>Gā(p.Asn1309Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
ENST00000334304.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADGRA3 | NM_145290.4 | c.3926A>G | p.Asn1309Ser | missense_variant | 19/19 | ENST00000334304.10 | NP_660333.2 | |
ADGRA3 | XM_047449703.1 | c.3335A>G | p.Asn1112Ser | missense_variant | 19/19 | XP_047305659.1 | ||
ADGRA3 | XM_047449704.1 | c.3335A>G | p.Asn1112Ser | missense_variant | 19/19 | XP_047305660.1 | ||
ADGRA3 | XM_011513811.3 | c.3248A>G | p.Asn1083Ser | missense_variant | 14/14 | XP_011512113.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADGRA3 | ENST00000334304.10 | c.3926A>G | p.Asn1309Ser | missense_variant | 19/19 | 1 | NM_145290.4 | ENSP00000334952 | P1 | |
ADGRA3 | ENST00000282943.9 | n.3497A>G | non_coding_transcript_exon_variant | 17/17 | 1 | |||||
ADGRA3 | ENST00000499527.6 | n.3623A>G | non_coding_transcript_exon_variant | 3/3 | 1 | |||||
ADGRA3 | ENST00000511051.5 | c.104+1343A>G | intron_variant, NMD_transcript_variant | 3 | ENSP00000424927 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250740Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135518
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461176Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726800
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 25, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ADGRA3-related conditions. This variant is present in population databases (rs144907660, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1309 of the ADGRA3 protein (p.Asn1309Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at