rs1654551
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000324041.6(KLK4):āc.64T>Gā(p.Ser22Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,613,798 control chromosomes in the GnomAD database, including 6,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S22W) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000324041.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLK4 | NM_004917.5 | c.64T>G | p.Ser22Ala | missense_variant, splice_region_variant | 3/6 | ENST00000324041.6 | NP_004908.4 | |
KLK4 | XM_011527545.4 | c.64T>G | p.Ser22Ala | missense_variant, splice_region_variant | 2/4 | XP_011525847.1 | ||
KLK4 | NM_001302961.2 | c.-234T>G | splice_region_variant, 5_prime_UTR_variant | 2/5 | NP_001289890.1 | |||
KLK4 | NR_126566.2 | n.62-17T>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLK4 | ENST00000324041.6 | c.64T>G | p.Ser22Ala | missense_variant, splice_region_variant | 3/6 | 1 | NM_004917.5 | ENSP00000326159 | P1 | |
KLK4 | ENST00000602148.1 | c.64T>G | p.Ser22Ala | missense_variant, splice_region_variant, NMD_transcript_variant | 2/5 | 1 | ENSP00000472091 | |||
KLK4 | ENST00000598305.5 | c.-217-17T>G | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | ENSP00000469963 | |||||
KLK4 | ENST00000596876.1 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.118 AC: 18000AN: 152060Hom.: 1456 Cov.: 31
GnomAD3 exomes AF: 0.0881 AC: 22104AN: 250912Hom.: 1189 AF XY: 0.0889 AC XY: 12067AN XY: 135728
GnomAD4 exome AF: 0.0812 AC: 118722AN: 1461620Hom.: 5503 Cov.: 36 AF XY: 0.0819 AC XY: 59582AN XY: 727086
GnomAD4 genome AF: 0.119 AC: 18046AN: 152178Hom.: 1464 Cov.: 31 AF XY: 0.118 AC XY: 8779AN XY: 74402
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | This variant is associated with the following publications: (PMID: 22970239) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at