rs1554736531

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014334.4(FRRS1L):​c.-38C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,002,548 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 (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

FRRS1L
NM_014334.4 5_prime_UTR

Scores

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.916
Variant links:
Genes affected
FRRS1L (HGNC:1362): (ferric chelate reductase 1 like) This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Mutations in this gene are associated with early infantile epileptic encephalopathy 37. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2350213).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FRRS1LNM_014334.4 linkuse as main transcriptc.-38C>T 5_prime_UTR_variant 1/5 ENST00000561981.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FRRS1LENST00000561981.5 linkuse as main transcriptc.-38C>T 5_prime_UTR_variant 1/51 NM_014334.4 P1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
0.00000199
AC:
2
AN:
1002548
Hom.:
0
Cov.:
31
AF XY:
0.00000211
AC XY:
1
AN XY:
474194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000229
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 37 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 13, 2022ClinVar contains an entry for this variant (Variation ID: 542870). This variant has not been reported in the literature in individuals affected with FRRS1L-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 39 of the FRRS1L protein (p.Ala39Val). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.022
Eigen_PC
Benign
-0.094
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.99
N
PrimateAI
Pathogenic
0.88
D
Sift4G
Uncertain
0.031
D
Polyphen
1.0
D
Vest4
0.16
MutPred
0.22
Loss of glycosylation at P37 (P = 0.0795);
MVP
0.74
MPC
0.083
ClinPred
0.81
D
GERP RS
2.5
Varity_R
0.034
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554736531; hg19: chr9-111929456; API