17-740186-G-A

Variant names:

• chr17-740186-G-A
• rs2740351
• NM_024792.3:c.409-319G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024792.3(TLCD3A):​c.409-319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,126 control chromosomes in the GnomAD database, including 34,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34118 hom., cov: 33)
• Consequence: TLCD3A NM_024792.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3A	NM_024792.3	MANE Select	c.409-319G>A		intron	N/A	NP_079068.1
	TLCD3A	NM_001318006.2		c.409-1115G>A		intron	N/A	NP_001304935.1
	TLCD3A	NM_001318007.2		c.207-319G>A		intron	N/A	NP_001304936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3A	ENST00000308278.13	TSL:1 MANE Select	c.409-319G>A		intron	N/A	ENSP00000312017.7
	TLCD3A	ENST00000301324.8	TSL:1	c.409-1115G>A		intron	N/A	ENSP00000301324.8
	TLCD3A	ENST00000572018.5	TSL:3	c.207-1115G>A		intron	N/A	ENSP00000460150.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100095 AN: 152008 Hom.: 34064 Cov.: 33

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100208 AN: 152126 Hom.: 34118 Cov.: 33 AF XY: 0.661 AC XY: 49123 AN XY: 74366

African (AFR) AF: 0.834 AC: 34626 AN: 41508

American (AMR) AF: 0.679 AC: 10387 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2188 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3647 AN: 5176

South Asian (SAS) AF: 0.640 AC: 3087 AN: 4820

European-Finnish (FIN) AF: 0.623 AC: 6582 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37726 AN: 67976

Other (OTH) AF: 0.661 AC: 1394 AN: 2108

Alfa AF: 0.602 Hom.: 77583

Bravo AF: 0.673

Asia WGS AF: 0.694 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2740351; hg19: chr17-643426; COSMIC: COSV56747366; COSMIC: COSV56747366;