11-120327583-A-G

Variant summary

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

The NM_001198672.2(TLCD5):​c.-162A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000226 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

TLCD5
NM_001198672.2 5_prime_UTR_premature_start_codon_gain

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92
Variant links:
Genes affected
TLCD5 (HGNC:28280): (TLC domain containing 5) 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=0.11851454).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLCD5NM_001198671.2 linkc.142A>G p.Ile48Val missense_variant Exon 2 of 3 ENST00000375095.3 NP_001185600.1 Q6ZRR5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLCD5ENST00000375095.3 linkc.142A>G p.Ile48Val missense_variant Exon 2 of 3 2 NM_001198671.2 ENSP00000364236.3 Q6ZRR5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251432
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461890
Hom.:
0
Cov.:
33
AF XY:
0.0000220
AC XY:
16
AN XY:
727246
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.208A>G (p.I70V) alteration is located in exon 2 (coding exon 1) of the TMEM136 gene. This alteration results from a A to G substitution at nucleotide position 208, causing the isoleucine (I) at amino acid position 70 to be replaced by a valine (V). 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
0.065
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.22
T;.;.
Eigen
Benign
-0.21
Eigen_PC
Benign
0.029
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
0.075
N;.;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.30
N;N;N
REVEL
Benign
0.28
Sift
Benign
0.79
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0040
B;B;B
Vest4
0.18
MutPred
0.52
Loss of sheet (P = 0.0025);.;.;
MVP
0.46
MPC
0.070
ClinPred
0.49
T
GERP RS
5.6
Varity_R
0.10
gMVP
0.15

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: rs770048393; hg19: chr11-120198292; API