rs1133782

Variant names:

• chr8-23144475-A-C
• rs1133782
• NM_003840.5:c.929T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-23144475-A-C
• chr8-23144475-A-G
• chr8-23144475-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003840.5(TNFRSF10D):​c.929T>G​(p.Leu310Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L310S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFRSF10D NM_003840.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 54 publications found

Genes affected

TNFRSF10D (HGNC:11907): (TNF receptor superfamily member 10d) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087771475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10D	NM_003840.5	c.929T>G	p.Leu310Trp	missense_variant	Exon 7 of 9	ENST00000312584.4	NP_003831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10D	ENST00000312584.4	c.929T>G	p.Leu310Trp	missense_variant	Exon 7 of 9	1	NM_003840.5	ENSP00000310263.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.2
DANN	Benign	0.63
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.63	T
PhyloP100		-3.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.17
Sift	Benign	0.046	D
Sift4G	Uncertain	0.013	D
Vest4		0.21
MutPred		0.21		Gain of sheet (P = 0.0149);
MVP		0.14
MPC		0.62
ClinPred		0.074	T
GERP RS		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.059
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1133782; hg19: chr8-23001988;