chr8-144354670-G-A

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

Scores

3
6
8

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.43
Variant links:
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]

Genome browser will be placed here

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
TMEM249NM_001280561.2 linkuse as main transcriptc.98C>T p.Ala33Val missense_variant 2/6 ENST00000696146.1
TMEM249NM_001252402.3 linkuse as main transcriptc.98C>T p.Ala33Val missense_variant 1/5
TMEM249NM_001252404.3 linkuse as main transcriptc.98C>T p.Ala33Val missense_variant 1/4
TMEM249NR_047684.3 linkuse as main transcriptn.262C>T non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM249ENST00000696146.1 linkuse as main transcriptc.98C>T p.Ala33Val missense_variant 2/6 NM_001280561.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1383300
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
682598
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000269
Hom.:
0

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 providedresearchDepartment of Molecular Bıology and Genetics, Istanbul Technical University-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.037
T;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.76
D
M_CAP
Pathogenic
0.45
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
2.0
M;.
MutationTaster
Benign
0.94
N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-2.3
N;D
Sift
Benign
0.36
T;D
Sift4G
Pathogenic
0.0
D;.
Polyphen
1.0
D;.
Vest4
0.36
MutPred
0.21
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
0.040
ClinPred
0.87
D
GERP RS
4.1
Varity_R
0.12
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs370391854; hg19: chr8-145578330; API