rs374675852
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005548.3(KARS1):c.-1G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,613,842 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005548.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KARS1 | NM_005548.3 | c.-1G>T | 5_prime_UTR_variant | Exon 1 of 14 | ENST00000302445.8 | NP_005539.1 | ||
KARS1 | NM_001130089.2 | c.-97G>T | 5_prime_UTR_variant | Exon 1 of 15 | NP_001123561.1 | |||
KARS1 | NM_001378148.1 | c.-583G>T | 5_prime_UTR_variant | Exon 1 of 14 | NP_001365077.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152260Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000249 AC: 62AN: 249378Hom.: 1 AF XY: 0.000237 AC XY: 32AN XY: 135288
GnomAD4 exome AF: 0.000121 AC: 177AN: 1461582Hom.: 1 Cov.: 31 AF XY: 0.000128 AC XY: 93AN XY: 727112
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74386
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.-1G>T variant in KARS has not been previously reported in individuals with hearing loss, but has been identified in 12/61810 of European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs37 4675852). This variant is located in the 5' UTR and its impact is unclear. In su mmary, the clinical significance of the c.-1G>T variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at