8-23191779-C-T

Variant names:

• chr8-23191779-C-T
• rs2230229
• NM_003844.4:c.1322G>A

Variant summary

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

The NM_003844.4(TNFRSF10A):​c.1322G>A​(p.Arg441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,614,030 control chromosomes in the GnomAD database, including 598,025 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 0.86 (56528 hom., cov: 31)
  • Exomes 𝑓: 0.86 (541497 hom.)
• Consequence: TNFRSF10A NM_003844.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 60 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.6099135E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 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.1322G>A	p.Arg441Lys	missense	Exon 10 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.1322G>A	p.Arg441Lys	missense	Exon 10 of 10	ENSP00000221132.3	O00220
	TNFRSF10A	ENST00000613472.1	TSL:1	c.848G>A	p.Arg283Lys	missense	Exon 9 of 9	ENSP00000480778.1	F8U8C0
	TNFRSF10A	ENST00000901503.1		c.1226G>A	p.Arg409Lys	missense	Exon 9 of 9	ENSP00000571562.1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130891 AN: 152030 Hom.: 56471 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.872

GnomAD2 exomes AF: 0.880 AC: 221372 AN: 251456 AF XY: 0.882

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.981

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.845

Gnomad OTH exome AF: 0.876

GnomAD4 exome AF: 0.860 AC: 1257001 AN: 1461882 Hom.: 541497 Cov.: 90 AF XY: 0.863 AC XY: 627266 AN XY: 727242

African (AFR) AF: 0.867 AC: 29033 AN: 33480

American (AMR) AF: 0.932 AC: 41698 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 23386 AN: 26136

East Asian (EAS) AF: 0.986 AC: 39153 AN: 39700

South Asian (SAS) AF: 0.951 AC: 82008 AN: 86258

European-Finnish (FIN) AF: 0.804 AC: 42929 AN: 53410

Middle Eastern (MID) AF: 0.888 AC: 5121 AN: 5768

European-Non Finnish (NFE) AF: 0.846 AC: 941138 AN: 1112010

Other (OTH) AF: 0.870 AC: 52535 AN: 60396

GnomAD4 genome AF: 0.861 AC: 131004 AN: 152148 Hom.: 56528 Cov.: 31 AF XY: 0.861 AC XY: 64034 AN XY: 74368

African (AFR) AF: 0.866 AC: 35942 AN: 41522

American (AMR) AF: 0.904 AC: 13823 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3082 AN: 3468

East Asian (EAS) AF: 0.979 AC: 5070 AN: 5178

South Asian (SAS) AF: 0.954 AC: 4597 AN: 4818

European-Finnish (FIN) AF: 0.792 AC: 8373 AN: 10576

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57363 AN: 67980

Other (OTH) AF: 0.874 AC: 1847 AN: 2114

Alfa AF: 0.855 Hom.: 263958

Bravo AF: 0.867

TwinsUK AF: 0.847 AC: 3142

ALSPAC AF: 0.844 AC: 3254

ESP6500AA AF: 0.856 AC: 3773

ESP6500EA AF: 0.846 AC: 7273

ExAC AF: 0.878 AC: 106618

Asia WGS AF: 0.959 AC: 3333 AN: 3478

EpiCase AF: 0.849

EpiControl AF: 0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.049
DANN	Benign	0.56
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	8.6e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-0.095
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.065
ClinPred		0.00023	T
GERP RS		-2.6
Varity_R		0.035
gMVP		0.41
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: rs2230229; hg19: chr8-23049292; COSMIC: COSV107279708; COSMIC: COSV107279708;