Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_032780.4(TMEM25):c.317A>T(p.Asn106Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N106S) has been classified as Uncertain significance.
TMEM25 (HGNC:25890): (transmembrane protein 25) Predicted to be involved in negative regulation of excitatory postsynaptic potential and regulation of protein stability. Predicted to be located in late endosome and lysosome. [provided by Alliance of Genome Resources, Apr 2022]
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33438
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26060
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39604
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53216
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111230
Other (OTH)
AF:
0.00
AC:
0
AN:
60280
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);.;Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);Loss of disorder (P = 0.0185);