rs753871349

Variant names:

• chr17-741347-C-A
• NM_024792.3:c.551C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-741347-C-A
• chr17-741347-C-G
• chr17-741347-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024792.3(TLCD3A):​c.551C>A​(p.Thr184Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 5.95

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD3A	NM_024792.3	c.551C>A	p.Thr184Lys	missense_variant	Exon 5 of 5	ENST00000308278.13	NP_079068.1
TLCD3A	NM_001318006.2	c.455C>A	p.Thr152Lys	missense_variant	Exon 4 of 4		NP_001304935.1
TLCD3A	NM_001318007.2	c.*85C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001304936.1
TLCD3A	NM_001318008.2	c.*43C>A		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.551C>A	p.Thr184Lys	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: 1461890 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.64
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.041	D;T
Polyphen		0.97	D;D
Vest4		0.49
MutPred		0.70		Gain of ubiquitination at T184 (P = 0.0203);.;
MVP		0.80
MPC		0.80
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.83

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: chr17-644587; COSMIC: COSV56747596; COSMIC: COSV56747596;