Genetic Variant TLCD3A:p.Val132Leu (chr17-738033-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024792.3(TLCD3A):c.394G>C(p.Val132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TLCD3A
NM_024792.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

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]

TLCD3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27043468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024792.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD3A	NM_024792.3	MANE Select	c.394G>C	p.Val132Leu	missense	Exon 3 of 5	NP_079068.1	Q8TBR7-2
TLCD3A	NM_001318006.2		c.394G>C	p.Val132Leu	missense	Exon 3 of 4	NP_001304935.1	Q8TBR7-1
TLCD3A	NM_001318007.2		c.207-2472G>C		intron	N/A	NP_001304936.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD3A	ENST00000308278.13	TSL:1 MANE Select	c.394G>C	p.Val132Leu	missense	Exon 3 of 5	ENSP00000312017.7	Q8TBR7-2
TLCD3A	ENST00000301324.8	TSL:1	c.394G>C	p.Val132Leu	missense	Exon 3 of 4	ENSP00000301324.8	Q8TBR7-1
TLCD3A	ENST00000572018.5	TSL:3	c.207-3268G>C		intron	N/A	ENSP00000460150.1	I3L336

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251428

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

M_CAP

Benign

0.080

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.028

MutationAssessor

Benign

1.5

PhyloP100

1.6

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.37

REVEL

Uncertain

0.36

Sift

Benign

0.41

Sift4G

Benign

0.59

Polyphen

0.99

Vest4

0.34

MutPred

0.55

Gain of catalytic residue at V132 (P = 0.0718)

MVP

0.55

MPC

0.50

ClinPred

0.25

GERP RS

5.8

Varity_R

0.058

gMVP

0.27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over