rs20577

Variant names:

• chr8-23224964-G-A
• rs20577
• NM_003844.4:c.98C>T

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.98C>T​(p.Thr33Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,600,150 control chromosomes in the GnomAD database, including 2,537 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.072 (1345 hom., cov: 30)
  • Exomes 𝑓: 0.0072 (1192 hom.)
• Consequence: TNFRSF10A NM_003844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 11 publications found

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

TNFRSF10A-DT (HGNC:52647): (TNFRSF10A divergent transcript)

ENSG00000250714 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050595105).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003844.4. 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
	TNFRSF10A	NM_003844.4	MANE Select	c.98C>T	p.Thr33Ile	missense	Exon 1 of 10	NP_003835.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	ENST00000221132.8	TSL:1 MANE Select	c.98C>T	p.Thr33Ile	missense	Exon 1 of 10	ENSP00000221132.3	O00220
	TNFRSF10A	ENST00000613472.1	TSL:1	c.31+67C>T		intron	N/A	ENSP00000480778.1	F8U8C0
	TNFRSF10A	ENST00000901503.1		c.98C>T	p.Thr33Ile	missense	Exon 1 of 9	ENSP00000571562.1

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10858 AN: 152084 Hom.: 1339 Cov.: 30

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0178 AC: 3959 AN: 222964 AF XY: 0.0132

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000671

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00719 AC: 10405 AN: 1447948 Hom.: 1192 Cov.: 31 AF XY: 0.00614 AC XY: 4416 AN XY: 719212

African (AFR) AF: 0.257 AC: 8517 AN: 33142

American (AMR) AF: 0.0123 AC: 533 AN: 43326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39060

South Asian (SAS) AF: 0.000261 AC: 22 AN: 84210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51496

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5754

European-Non Finnish (NFE) AF: 0.000321 AC: 355 AN: 1105404

Other (OTH) AF: 0.0150 AC: 898 AN: 59742

GnomAD4 genome AF: 0.0715 AC: 10887 AN: 152202 Hom.: 1345 Cov.: 30 AF XY: 0.0686 AC XY: 5108 AN XY: 74426

African (AFR) AF: 0.250 AC: 10377 AN: 41482

American (AMR) AF: 0.0234 AC: 358 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68014

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0250 Hom.: 435

Bravo AF: 0.0816

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.222 AC: 977

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0218 AC: 2634

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.4
DANN	Benign	0.90
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.53
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.042
MPC		0.077
ClinPred		0.012	T
GERP RS		0.69
PromoterAI		0.11	Neutral
Varity_R		0.11
gMVP		0.23
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: rs20577; hg19: chr8-23082477; COSMIC: COSV55326212; COSMIC: COSV55326212;