Genetic Variant NM_024792.3:c.200C>T (chr17-733175-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024792.3(TLCD3A):c.200C>T(p.Thr67Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,559,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TLCD3A
NM_024792.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.271

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096128225).

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.200C>T	p.Thr67Ile	missense	Exon 2 of 5	NP_079068.1	Q8TBR7-2
TLCD3A	NM_001318006.2		c.200C>T	p.Thr67Ile	missense	Exon 2 of 4	NP_001304935.1	Q8TBR7-1
TLCD3A	NM_001318007.2		c.200C>T	p.Thr67Ile	missense	Exon 2 of 4	NP_001304936.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD3A	ENST00000308278.13	TSL:1 MANE Select	c.200C>T	p.Thr67Ile	missense	Exon 2 of 5	ENSP00000312017.7	Q8TBR7-2
TLCD3A	ENST00000301324.8	TSL:1	c.200C>T	p.Thr67Ile	missense	Exon 2 of 4	ENSP00000301324.8	Q8TBR7-1
TLCD3A	ENST00000572018.5	TSL:3	c.200C>T	p.Thr67Ile	missense	Exon 2 of 3	ENSP00000460150.1	I3L336

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000534

AC:

AN:

168616

AF XY:

0.0000538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1407802

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

696970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30524

American (AMR)

AF:

0.00

AC:

AN:

38146

Ashkenazi Jewish (ASJ)

AF:

0.000927

AC:

AN:

24820

East Asian (EAS)

AF:

0.00

AC:

AN:

34698

South Asian (SAS)

AF:

0.00

AC:

AN:

79586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00000644

AC:

AN:

1086784

Other (OTH)

AF:

0.000137

AC:

AN:

58198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000905

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000837

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

Benign

0.18

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.6

PhyloP100

0.27

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.26

Sift

Benign

0.42

Sift4G

Benign

0.39

Polyphen

0.90

Vest4

0.32

MutPred

0.32

Gain of sheet (P = 0.0344)

MVP

0.66

MPC

0.38

ClinPred

0.93

GERP RS

0.46

PromoterAI

0.0047

Neutral

(source)

Varity_R

0.075

gMVP

0.17

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over