17-741424-A-G

Position:

• chr17-741424-A-G

Variant summary

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

The ENST00000308278.13(TLCD3A):​c.628A>G​(p.Ser210Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLCD3A ENST00000308278.13 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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=0.29394925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLCD3A	NM_024792.3	c.628A>G	p.Ser210Gly	missense_variant	5/5	ENST00000308278.13	NP_079068.1
TLCD3A	NM_001318006.2	c.532A>G	p.Ser178Gly	missense_variant	4/4		NP_001304935.1
TLCD3A	NM_001318007.2	c.*162A>G		3_prime_UTR_variant	4/4		NP_001304936.1
TLCD3A	NM_001318008.2	c.*120A>G		3_prime_UTR_variant	3/3		NP_001304937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLCD3A	ENST00000308278.13	c.628A>G	p.Ser210Gly	missense_variant	5/5	1	NM_024792.3	ENSP00000312017.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.628A>G (p.S210G) alteration is located in exon 5 (coding exon 5) of the FAM57A gene. This alteration results from a A to G substitution at nucleotide position 628, causing the serine (S) at amino acid position 210 to be replaced by a glycine (G). 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	Benign	0.071
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.74	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.63	P;P
Vest4		0.13
MutPred		0.57		Loss of helix (P = 0.1299);.;
MVP		0.88
MPC		0.42
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.15
gMVP		0.45

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: chr17-644664;