NM_003840.5:c.955-1006T>G

Variant names:

• chr8-23139266-A-C
• rs4278155
• NM_003840.5:c.955-1006T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003840.5(TNFRSF10D):​c.955-1006T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,844 control chromosomes in the GnomAD database, including 4,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4590 hom., cov: 32)
• Consequence: TNFRSF10D NM_003840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

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.955-1006T>G		intron	N/A	NP_003831.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10D	ENST00000312584.4	TSL:1 MANE Select	c.955-1006T>G		intron	N/A	ENSP00000310263.3	Q9UBN6
	TNFRSF10D	ENST00000870290.1		c.1027-1006T>G		intron	N/A	ENSP00000540349.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35203 AN: 151726 Hom.: 4573 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35274 AN: 151844 Hom.: 4590 Cov.: 32 AF XY: 0.237 AC XY: 17580 AN XY: 74246

African (AFR) AF: 0.283 AC: 11668 AN: 41230

American (AMR) AF: 0.362 AC: 5523 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2395 AN: 5172

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1831 AN: 10594

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11534 AN: 67976

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.197 Hom.: 14999

Bravo AF: 0.248

Asia WGS AF: 0.351 AC: 1217 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		0.099
Mutation Taster		=100/0	polymorphism (auto)

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: rs4278155; hg19: chr8-22996779;