chr8-144354670-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001280561.2(TMEM249):c.98C>T(p.Ala33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TMEM249
NM_001280561.2 missense
NM_001280561.2 missense
Scores
3
6
8
Clinical Significance
Conservation
PhyloP100: 3.43
Genes affected
TMEM249 (HGNC:44155): (transmembrane protein 249) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
SLC52A2 (HGNC:30224): (solute carrier family 52 member 2) This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32949153).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM249 | NM_001280561.2 | c.98C>T | p.Ala33Val | missense_variant | 2/6 | ENST00000696146.1 | |
TMEM249 | NM_001252402.3 | c.98C>T | p.Ala33Val | missense_variant | 1/5 | ||
TMEM249 | NM_001252404.3 | c.98C>T | p.Ala33Val | missense_variant | 1/4 | ||
TMEM249 | NR_047684.3 | n.262C>T | non_coding_transcript_exon_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM249 | ENST00000696146.1 | c.98C>T | p.Ala33Val | missense_variant | 2/6 | NM_001280561.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1383300Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 682598
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1383300
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
682598
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Epidermolysis bullosa simplex with nail dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | research | Department of Molecular Bıology and Genetics, Istanbul Technical University | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D
Sift
Benign
T;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at