chr11-120330271-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001198671.2(TLCD5):​c.494T>A​(p.Val165Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,403,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TLCD5
NM_001198671.2 missense

Scores

6
11
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLCD5NM_001198671.2 linkuse as main transcriptc.494T>A p.Val165Glu missense_variant 3/3 ENST00000375095.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLCD5ENST00000375095.3 linkuse as main transcriptc.494T>A p.Val165Glu missense_variant 3/32 NM_001198671.2 P1Q6ZRR5-1
TLCD5ENST00000529187.1 linkuse as main transcriptc.339-136T>A intron_variant 1 Q6ZRR5-4
TLCD5ENST00000314475.6 linkuse as main transcriptc.560T>A p.Val187Glu missense_variant 3/32 Q6ZRR5-3
TLCD5ENST00000531346.1 linkuse as main transcriptn.368T>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000179
AC:
3
AN:
167174
Hom.:
0
AF XY:
0.0000113
AC XY:
1
AN XY:
88186
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000119
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1403538
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
693168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000554
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsAug 09, 2021The c.560T>A (p.V187E) alteration is located in exon 3 (coding exon 2) of the TMEM136 gene. This alteration results from a T to A substitution at nucleotide position 560, causing the valine (V) at amino acid position 187 to be replaced by a glutamic acid (E). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
D;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.083
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.38
D
MutationAssessor
Uncertain
2.4
M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.76
MutPred
0.68
Loss of loop (P = 0.0145);.;
MVP
0.83
MPC
0.33
ClinPred
0.86
D
GERP RS
4.9
Varity_R
0.76
gMVP
0.92

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: rs1321227509; hg19: chr11-120200980; API