NM_014334.4:c.178G>C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_014334.4(FRRS1L):c.178G>C(p.Asp60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,344,900 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D60Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_014334.4 missense
Scores
Clinical Significance
Conservation
Publications
- developmental and epileptic encephalopathy, 37Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- autosomal recessive non-syndromic intellectual disabilityInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRRS1L | ENST00000561981.5 | c.178G>C | p.Asp60His | missense_variant | Exon 1 of 5 | 1 | NM_014334.4 | ENSP00000477141.2 | ||
FRRS1L | ENST00000644747.1 | n.43G>C | non_coding_transcript_exon_variant | Exon 1 of 4 | ENSP00000493964.1 | |||||
FRRS1L | ENST00000642299.1 | n.-30G>C | upstream_gene_variant | ENSP00000495137.1 |
Frequencies
GnomAD3 genomes AF: 0.0000467 AC: 7AN: 149866Hom.: 0 Cov.: 25 show subpopulations
GnomAD2 exomes AF: 0.000109 AC: 7AN: 64462 AF XY: 0.000188 show subpopulations
GnomAD4 exome AF: 0.0000285 AC: 34AN: 1194926Hom.: 0 Cov.: 33 AF XY: 0.0000396 AC XY: 23AN XY: 581432 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000467 AC: 7AN: 149974Hom.: 0 Cov.: 25 AF XY: 0.0000957 AC XY: 7AN XY: 73168 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 37 Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 111 of the FRRS1L protein (p.Asp111His). This variant is present in population databases (rs772506414, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FRRS1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 572403). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at