rs1191779627

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014334.4(FRRS1L):ā€‹c.869T>Cā€‹(p.Met290Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,144 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)

Consequence

FRRS1L
NM_014334.4 missense

Scores

7
4
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRRS1LNM_014334.4 linkc.869T>C p.Met290Thr missense_variant Exon 5 of 5 ENST00000561981.5 NP_055149.3 Q9P0K9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRRS1LENST00000561981.5 linkc.869T>C p.Met290Thr missense_variant Exon 5 of 5 1 NM_014334.4 ENSP00000477141.2 Q9P0K9
FRRS1LENST00000644747.1 linkn.*487T>C non_coding_transcript_exon_variant Exon 4 of 4 ENSP00000493964.1 A0A2R8Y4E4
FRRS1LENST00000644747.1 linkn.*487T>C 3_prime_UTR_variant Exon 4 of 4 ENSP00000493964.1 A0A2R8Y4E4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.059
T
Eigen
Uncertain
0.58
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.91
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.97
D
Vest4
0.84
MutPred
0.26
Gain of glycosylation at M341 (P = 0.0264);
MVP
0.72
MPC
0.30
ClinPred
0.97
D
GERP RS
6.0
Varity_R
0.47
gMVP
0.83

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: rs1191779627; hg19: chr9-111899748; API