7-100106862-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004722.4(AP4M1):c.1342G>A(p.Ala448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,613,332 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A448A) has been classified as Likely benign.
Frequency
Consequence
NM_004722.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000264 AC: 66AN: 250032Hom.: 1 AF XY: 0.000281 AC XY: 38AN XY: 135412
GnomAD4 exome AF: 0.000250 AC: 366AN: 1461092Hom.: 2 Cov.: 34 AF XY: 0.000267 AC XY: 194AN XY: 726884
GnomAD4 genome AF: 0.000243 AC: 37AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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In silico analysis supports that this missense variant does not alter protein structure/function -
not specified Uncertain:1
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Hereditary spastic paraplegia Uncertain:1
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AP4M1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary spastic paraplegia 50 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at