3-190429725-T-C

Variant summary

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

The NM_207316.3(TMEM207):ā€‹c.311A>Gā€‹(p.Glu104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TMEM207
NM_207316.3 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08
Variant links:
Genes affected
TMEM207 (HGNC:33705): (transmembrane protein 207) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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/exons MANE Protein UniProt
TMEM207NM_207316.3 linkuse as main transcriptc.311A>G p.Glu104Gly missense_variant 5/5 ENST00000354905.3 NP_997199.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM207ENST00000354905.3 linkuse as main transcriptc.311A>G p.Glu104Gly missense_variant 5/51 NM_207316.3 ENSP00000346981 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1452374
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722038
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:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 16, 2024The c.311A>G (p.E104G) alteration is located in exon 5 (coding exon 5) of the TMEM207 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the glutamic acid (E) at amino acid position 104 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.089
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
0.88
N
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-7.0
D
REVEL
Benign
0.19
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.53
MutPred
0.34
Gain of glycosylation at Y101 (P = 0.0042);
MVP
0.45
MPC
0.16
ClinPred
0.99
D
GERP RS
4.6
Varity_R
0.73
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs1719649527; hg19: chr3-190147514; API