10-13278305-A-AGAT
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM4_SupportingBP6
The NM_006214.4(PHYH):c.1012_1013insATC(p.Asn337_Leu338insHis) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00213 in 1,609,052 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L338L) has been classified as Likely benign.
Frequency
Consequence
NM_006214.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHYH | NM_006214.4 | c.1012_1013insATC | p.Asn337_Leu338insHis | inframe_insertion | 9/9 | ENST00000263038.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.1012_1013insATC | p.Asn337_Leu338insHis | inframe_insertion | 9/9 | 1 | NM_006214.4 | P1 | |
PHYH | ENST00000396913.6 | c.712_713insATC | p.Asn237_Leu238insHis | inframe_insertion | 8/8 | 5 | |||
PHYH | ENST00000396920.7 | c.961_962insATC | p.Asn320_Leu321insHis | inframe_insertion | 9/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00160 AC: 243AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00204 AC: 513AN: 251408Hom.: 1 AF XY: 0.00205 AC XY: 279AN XY: 135890
GnomAD4 exome AF: 0.00218 AC: 3182AN: 1456730Hom.: 5 Cov.: 29 AF XY: 0.00209 AC XY: 1513AN XY: 725128
GnomAD4 genome ? AF: 0.00160 AC: 243AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 07, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | PHYH: BS2 - |
Nonsyndromic cleft lip palate Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Mar 27, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 01, 2024 | Variant summary: PHYH c.1010_1012dupATC (p.Asn337_Leu338insHis) results in an in-frame insertion that is predicted to insert *** amino acids into the encoded protein. The variant allele was found at a frequency of 0.002 in 251408 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in PHYH causing Phytanic Acid Storage Disease (0.002 vs ND), allowing no conclusion about variant significance. c.1010_1012dupATC has been reported in the literature in individuals affected with Phytanic Acid Storage Disease. These report(s) do not provide unequivocal conclusions about association of the variant with Phytanic Acid Storage Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 444210). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at