Variant 17-732687-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024792.3(TLCD3A):c.40G>A(p.Gly14Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000302 in 1,423,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TLCD3A
NM_024792.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLCD3A	NM_024792.3 link	c.40G>A	p.Gly14Arg	missense_variant	1/5	ENST00000308278.13	NP_079068.1	Q8TBR7-2
TLCD3A	NM_001318006.2 link	c.40G>A	p.Gly14Arg	missense_variant	1/4		NP_001304935.1	Q8TBR7-1
TLCD3A	NM_001318007.2 link	c.40G>A	p.Gly14Arg	missense_variant	1/4		NP_001304936.1	Q8TBR7
TLCD3A	NM_001318008.2 link	c.40G>A	p.Gly14Arg	missense_variant	1/3		NP_001304937.1	Q8TBR7I3L336

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLCD3A	ENST00000308278.13 link	c.40G>A	p.Gly14Arg	missense_variant	1/5	1	NM_024792.3	ENSP00000312017.7		Q8TBR7-2

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

70368

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

40700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000390

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000291

AC:

AN:

1271254

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

625682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000386

Gnomad4 AMR exome

AF:

0.000381

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:

0.0000216

Gnomad4 OTH exome

AF:

0.0000775

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000475

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.40G>A (p.G14R) alteration is located in exon 1 (coding exon 1) of the FAM57A gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.67

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.9

M;.;M

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.1

D;.;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.029

D;.;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.88

P;.;P

Vest4

0.74

MutPred

0.70

Gain of MoRF binding (P = 0.0467);Gain of MoRF binding (P = 0.0467);Gain of MoRF binding (P = 0.0467);

MVP

0.33

MPC

0.76

ClinPred

0.56

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.46

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over