21-44573947-G-A
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_198687.2(KRTAP10-4):c.189G>A(p.Val63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 151,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0026 ( 0 hom., cov: 47)
Exomes 𝑓: 0.0013 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
KRTAP10-4
NM_198687.2 synonymous
NM_198687.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.513
Genes affected
KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]
TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 21-44573947-G-A is Benign according to our data. Variant chr21-44573947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652763.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.513 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-4 | NM_198687.2 | c.189G>A | p.Val63= | synonymous_variant | 1/1 | ENST00000400374.4 | |
TSPEAR | NM_144991.3 | c.83-5942C>T | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-5942C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-4 | ENST00000400374.4 | c.189G>A | p.Val63= | synonymous_variant | 1/1 | NM_198687.2 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-5942C>T | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-5942C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00261 AC: 395AN: 151132Hom.: 0 Cov.: 47
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GnomAD3 exomes AF: 0.00176 AC: 419AN: 237396Hom.: 3 AF XY: 0.00172 AC XY: 223AN XY: 129586
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00127 AC: 1837AN: 1449162Hom.: 1 Cov.: 164 AF XY: 0.00136 AC XY: 979AN XY: 719696
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GnomAD4 genome AF: 0.00260 AC: 394AN: 151252Hom.: 0 Cov.: 47 AF XY: 0.00253 AC XY: 187AN XY: 73884
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | KRTAP10-4: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at