chr17-741410-G-T

Variant names:

• chr17-741410-G-T
• NM_024792.3:c.614G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024792.3(TLCD3A):​c.614G>T​(p.Arg205Leu) 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 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TLCD3A NM_024792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3169272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD3A	NM_024792.3	c.614G>T	p.Arg205Leu	missense_variant	Exon 5 of 5	ENST00000308278.13	NP_079068.1
TLCD3A	NM_001318006.2	c.518G>T	p.Arg173Leu	missense_variant	Exon 4 of 4		NP_001304935.1
TLCD3A	NM_001318007.2	c.*148G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001304936.1
TLCD3A	NM_001318008.2	c.*106G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001304937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD3A	ENST00000308278.13	c.614G>T	p.Arg205Leu	missense_variant	Exon 5 of 5	1	NM_024792.3	ENSP00000312017.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.65	D;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.55	P;P
Vest4		0.35
MutPred		0.63		Loss of helix (P = 0.0093);.;
MVP		0.75
MPC		0.39
ClinPred		0.97	D
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.48

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.

Other links and lift over

hg19: chr17-644650;