8-23137993-C-A

Variant names:

• chr8-23137993-C-A
• rs771299446
• NM_003840.5:c.1038G>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.1038G>T​(p.Leu346Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFRSF10D NM_003840.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.15
• Publications: 0 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=0.13228154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003840.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10D	NM_003840.5	MANE Select	c.1038G>T	p.Leu346Phe	missense	Exon 9 of 9	NP_003831.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10D	ENST00000312584.4	TSL:1 MANE Select	c.1038G>T	p.Leu346Phe	missense	Exon 9 of 9	ENSP00000310263.3	Q9UBN6
	TNFRSF10D	ENST00000870290.1		c.1110G>T	p.Leu370Phe	missense	Exon 9 of 9	ENSP00000540349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.11
DANN	Benign	0.72
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
PhyloP100		-2.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.082
Sift	Benign	0.25	T
Sift4G	Benign	0.17	T
Vest4		0.084
MutPred		0.25		Loss of helix (P = 0.0167)
MVP		0.31
MPC		0.14
ClinPred		0.091	T
GERP RS		-1.4
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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: rs771299446; hg19: chr8-22995506;