1-27322292-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000608611(TMEM222):​c.-5C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,561,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM222
ENST00000608611 5_prime_UTR_premature_start_codon_gain

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.337
Variant links:
Genes affected
TMEM222 (HGNC:25363): (transmembrane protein 222) 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16367489).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM222NM_032125.3 linkc.95C>T p.Thr32Met missense_variant Exon 1 of 6 ENST00000374076.9 NP_115501.2 Q9H0R3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM222ENST00000374076.9 linkc.95C>T p.Thr32Met missense_variant Exon 1 of 6 1 NM_032125.3 ENSP00000363189.4 Q9H0R3-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
AF:
0.00000142
AC:
2
AN:
1409458
Hom.:
0
Cov.:
31
AF XY:
0.00000143
AC XY:
1
AN XY:
698814
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:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.23e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 31, 2024
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: TMEM222 c.95C>T (p.Thr32Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.95C>T in individuals affected with Neurodevelopmental Disorder With Motor And Speech Delay And Behavioral Abnormalities and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.78
T;.
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
0.030
.;N
REVEL
Benign
0.089
Sift
Benign
0.15
.;T
Sift4G
Benign
0.20
T;T
Polyphen
0.93
P;P
Vest4
0.33
MutPred
0.17
Loss of phosphorylation at T32 (P = 0.0169);Loss of phosphorylation at T32 (P = 0.0169);
MVP
0.19
MPC
0.40
ClinPred
0.56
D
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.030
gMVP
0.43

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: rs1285526688; hg19: chr1-27648783; API