rs149887215
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_014053.4(FLVCR1):c.1657T>G(p.Ser553Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,613,098 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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_014053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLVCR1 | NM_014053.4 | c.1657T>G | p.Ser553Ala | missense_variant | 10/10 | ENST00000366971.9 | |
FLVCR1 | XR_007059232.1 | n.1724T>G | non_coding_transcript_exon_variant | 9/10 | |||
FLVCR1 | XR_247024.4 | n.1835T>G | non_coding_transcript_exon_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLVCR1 | ENST00000366971.9 | c.1657T>G | p.Ser553Ala | missense_variant | 10/10 | 1 | NM_014053.4 | P1 | |
FLVCR1 | ENST00000419102.1 | c.1054T>G | p.Ser352Ala | missense_variant | 9/9 | 5 | |||
FLVCR1 | ENST00000483790.1 | n.484T>G | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000565 AC: 86AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251390Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135870
GnomAD4 exome AF: 0.0000999 AC: 146AN: 1460850Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 66AN XY: 726830
GnomAD4 genome ? AF: 0.000604 AC: 92AN: 152248Hom.: 2 Cov.: 32 AF XY: 0.000631 AC XY: 47AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | FLVCR1: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2016 | The S553A variant in the FLVCR1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports S553A was observed with a frequency of 0.23% (10/4406) alleles from individuals of African American background, indicating it may be a rare variant in this population. The S553A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S553A as a variant of uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 02, 2020 | - - |
Posterior column ataxia-retinitis pigmentosa syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2021 | The c.1657T>G (p.S553A) alteration is located in exon 10 (coding exon 10) of the FLVCR1 gene. This alteration results from a T to G substitution at nucleotide position 1657, causing the serine (S) at amino acid position 553 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | May 08, 2019 | - - |
FLVCR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 2022 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at