chr4-88678013-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_014606.3(HERC3):c.2075T>G(p.Leu692Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L692V) has been classified as Uncertain significance.
Frequency
Consequence
NM_014606.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC3 | NM_014606.3 | c.2075T>G | p.Leu692Arg | missense_variant | 19/26 | ENST00000402738.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC3 | ENST00000402738.6 | c.2075T>G | p.Leu692Arg | missense_variant | 19/26 | 1 | NM_014606.3 | P1 | |
HERC3 | ENST00000264345.7 | c.2075T>G | p.Leu692Arg | missense_variant | 17/24 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250940Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135630
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461552Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727098
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2023 | The c.2075T>G (p.L692R) alteration is located in exon 19 (coding exon 17) of the HERC3 gene. This alteration results from a T to G substitution at nucleotide position 2075, causing the leucine (L) at amino acid position 692 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at