NM_006214.4:c.1010_1012dupATC
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS2
The NM_006214.4(PHYH):c.1010_1012dupATC(p.Asn337_Leu338insHis) variant causes a conservative 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).
Frequency
Consequence
NM_006214.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PHYH | ENST00000263038.9 | c.1010_1012dupATC | p.Asn337_Leu338insHis | conservative_inframe_insertion | Exon 9 of 9 | 1 | NM_006214.4 | ENSP00000263038.4 | ||
PHYH | ENST00000396920.7 | c.959_961dupATC | p.Asn320_Leu321insHis | conservative_inframe_insertion | Exon 9 of 9 | 5 | ENSP00000380126.3 | |||
PHYH | ENST00000396913.6 | c.710_712dupATC | p.Asn237_Leu238insHis | conservative_inframe_insertion | Exon 8 of 8 | 5 | ENSP00000380121.2 |
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
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PHYH: BS2 -
Nonsyndromic cleft lip palate Pathogenic:1
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not specified Uncertain:1
Variant summary: PHYH c.1010_1012dupATC (p.Asn337_Leu338insHis) results in an in-frame insertion that is predicted to insert 1 amino acid 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 homozygote. c.1010_1012dupATC has been reported in the literature in individuals affected with retinal disease or nonsyndromic cleft lip and palate without strong evidence of causality (Watson_2014, Aylward_2016, Dieriro_2020). These reports 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. The following publications have been ascertained in the context of this evaluation (PMID: 25133751, 27229527, 32483926). ClinVar contains an entry for this variant (Variation ID: 444210). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Optic atrophy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at