chr17-44012098-G-T

Variant summary

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

The NM_032376.4(TMEM101):​c.604C>A​(p.Leu202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

TMEM101
NM_032376.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. 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=0.10077977).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM101NM_032376.4 linkuse as main transcriptc.604C>A p.Leu202Ile missense_variant 4/4 ENST00000206380.8 NP_115752.1 Q96IK0
TMEM101NM_001304813.2 linkuse as main transcriptc.430C>A p.Leu144Ile missense_variant 5/5 NP_001291742.1 Q96IK0B4DFS4
TMEM101NM_001304814.2 linkuse as main transcriptc.430C>A p.Leu144Ile missense_variant 5/5 NP_001291743.1 Q96IK0B4DFS4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM101ENST00000206380.8 linkuse as main transcriptc.604C>A p.Leu202Ile missense_variant 4/41 NM_032376.4 ENSP00000206380.3 Q96IK0
TMEM101ENST00000589334.5 linkuse as main transcriptc.604C>A p.Leu202Ile missense_variant 5/55 ENSP00000468025.1 Q96IK0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000478
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152352
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000473

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 GeneticsMar 28, 2024The c.604C>A (p.L202I) alteration is located in exon 4 (coding exon 4) of the TMEM101 gene. This alteration results from a C to A substitution at nucleotide position 604, causing the leucine (L) at amino acid position 202 to be replaced by an isoleucine (I). 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
0.085
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.045
T;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.80
.;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.95
.;N
REVEL
Benign
0.010
Sift
Benign
0.30
.;T
Sift4G
Benign
0.50
T;T
Polyphen
0.10
B;B
Vest4
0.24
MutPred
0.34
Gain of catalytic residue at L202 (P = 0.0524);Gain of catalytic residue at L202 (P = 0.0524);
MVP
0.22
MPC
1.2
ClinPred
0.27
T
GERP RS
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.062
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42089466; COSMIC: COSV99243999; COSMIC: COSV99243999; API