rs141305698

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024792.3(TLCD3A):​c.455C>A​(p.Thr152Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.8e-7 ( 0 hom. )

Consequence

TLCD3A
NM_024792.3 missense

Scores

3
10
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0130
Variant links:
Genes affected
TLCD3A (HGNC:29646): (TLC domain containing 3A) The protein encoded by this gene is a membrane-associated protein that promotes lung carcinogenesis. The encoded protein may be involved in amino acid transport and glutathione metabolism since it can interact with a solute carrier family member (SLC3A2) and an isoform of gamma-glutamyltranspeptidase-like 3. An alternatively spliced variant encoding a protein that lacks a 32 aa internal segment showed the opposite effect, inhibiting lung cancer cell growth. Knockdown of this gene also inhibited lung carcinogenesis and tumor cell growth. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLCD3ANM_024792.3 linkc.455C>A p.Thr152Lys missense_variant Exon 4 of 5 ENST00000308278.13 NP_079068.1 Q8TBR7-2
TLCD3ANM_001318007.2 linkc.253C>A p.Arg85Arg synonymous_variant Exon 3 of 4 NP_001304936.1 Q8TBR7
TLCD3ANM_001318006.2 linkc.409-750C>A intron_variant Intron 3 of 3 NP_001304935.1 Q8TBR7-1
TLCD3ANM_001318008.2 linkc.207-750C>A intron_variant Intron 2 of 2 NP_001304937.1 Q8TBR7I3L336

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLCD3AENST00000308278.13 linkc.455C>A p.Thr152Lys missense_variant Exon 4 of 5 1 NM_024792.3 ENSP00000312017.7 Q8TBR7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461762
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.60
D
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Uncertain
0.15
D
MutationAssessor
Uncertain
2.7
M
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.9
D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.014
D
Polyphen
0.81
P
Vest4
0.75
MutPred
0.67
Gain of ubiquitination at T152 (P = 0.017);
MVP
0.69
MPC
0.74
ClinPred
0.96
D
GERP RS
2.0
Varity_R
0.16
gMVP
0.78

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: rs141305698; hg19: chr17-643791; API