6-109741502-A-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_014845.6(FIG4):c.834A>T(p.Lys278Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,613,222 control chromosomes in the GnomAD database, including 1 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).
Frequency
Consequence
NM_014845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000299 AC: 75AN: 250824Hom.: 0 AF XY: 0.000288 AC XY: 39AN XY: 135532
GnomAD4 exome AF: 0.000213 AC: 311AN: 1460978Hom.: 1 Cov.: 30 AF XY: 0.000220 AC XY: 160AN XY: 726848
GnomAD4 genome AF: 0.000282 AC: 43AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74440
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:3
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See Variant Classification Assertion Criteria. -
FIG4: PM2 -
BP4 -
Charcot-Marie-Tooth disease type 4J Uncertain:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Amyotrophic lateral sclerosis type 11 Uncertain:1Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Bilateral parasagittal parieto-occipital polymicrogyria Uncertain:1
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Yunis-Varon syndrome Uncertain:1
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not specified Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
FIG4-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). -
Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at