rs1654551
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004917.5(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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. S22S) has been classified as Benign.
Frequency
Consequence
NM_004917.5 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 |
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 | ENSP00000326159.1 | ||
KLK4 | ENST00000602148.1 | n.64T>G | splice_region_variant, non_coding_transcript_exon_variant | 2/5 | 1 | ENSP00000472091.1 | ||||
KLK4 | ENST00000598305.5 | n.-217-17T>G | intron_variant | 1 | ENSP00000469963.1 | |||||
KLK4 | ENST00000596876.1 | n.-30T>G | 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