chr3-172514982-G-C

Variant names:

• chr3-172514982-G-C
• NM_003810.4:c.149C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003810.4(TNFSF10):​c.149C>G​(p.Ser50Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,848 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: 0.0000075 (0 hom.)
• Consequence: TNFSF10 NM_003810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2221249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.149C>G	p.Ser50Cys	missense_variant	Exon 2 of 5	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.149C>G	p.Ser50Cys	missense_variant	Exon 2 of 3		NP_001177871.1
TNFSF10	NR_033994.2	n.195C>G		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.149C>G	p.Ser50Cys	missense_variant	Exon 2 of 5	1	NM_003810.4	ENSP00000241261.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727232

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: 0.00000809

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D;.
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.17
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;.
Vest4		0.26
MutPred		0.46		Loss of disorder (P = 6e-04);Loss of disorder (P = 6e-04);
MVP		0.49
MPC		0.33
ClinPred		0.87	D
GERP RS		1.8
Varity_R		0.098
gMVP		0.55

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: chr3-172232772;