dbSNP rs1974088406: TLCD3A:p.Cys35Ser (chr17-732750-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_024792.3(TLCD3A):c.103T>A(p.Cys35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,302,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

TLCD3A
NM_024792.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.473

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 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=0.20880726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD3A	NM_024792.3 link	c.103T>A	p.Cys35Ser	missense_variant	Exon 1 of 5	ENST00000308278.13	NP_079068.1	Q8TBR7-2
TLCD3A	NM_001318006.2 link	c.103T>A	p.Cys35Ser	missense_variant	Exon 1 of 4		NP_001304935.1	Q8TBR7-1
TLCD3A	NM_001318007.2 link	c.103T>A	p.Cys35Ser	missense_variant	Exon 1 of 4		NP_001304936.1	Q8TBR7
TLCD3A	NM_001318008.2 link	c.103T>A	p.Cys35Ser	missense_variant	Exon 1 of 3		NP_001304937.1	Q8TBR7I3L336

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD3A	ENST00000308278.13 link	c.103T>A	p.Cys35Ser	missense_variant	Exon 1 of 5	1	NM_024792.3	ENSP00000312017.7		Q8TBR7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.68e-7

AC:

AN:

1302590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

641810

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.64e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.052

T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.61

T;T;T

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

M;.;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.074

T;.;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.079

B;.;B

Vest4

0.24

MutPred

0.53

Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);

MVP

0.076

MPC

0.24

ClinPred

0.49

GERP RS

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.088

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over