20-63696799-T-G

Variant names:

• chr20-63696799-T-G
• NM_003823.4:c.32T>G

Variant summary

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

The NM_003823.4(TNFRSF6B):​c.32T>G​(p.Leu11Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L11L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TNFRSF6B NM_003823.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.466
• Publications: 0 publications found

Genes affected

TNFRSF6B (HGNC:11921): (TNF receptor superfamily member 6b) This gene belongs to the tumor necrosis factor receptor superfamily. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript. [provided by RefSeq, Feb 2011]

RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

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=0.14172187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003823.4. 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
	TNFRSF6B	NM_003823.4	MANE Select	c.32T>G	p.Leu11Arg	missense	Exon 1 of 3	NP_003814.1	O95407
	RTEL1-TNFRSF6B	NR_037882.1		n.4766T>G		non_coding_transcript_exon	Exon 36 of 38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF6B	ENST00000369996.3	TSL:1 MANE Select	c.32T>G	p.Leu11Arg	missense	Exon 1 of 3	ENSP00000359013.1	O95407
	RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1371T>G		non_coding_transcript_exon	Exon 33 of 35	ENSP00000457428.1	D6RA96
	RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1371T>G		3_prime_UTR	Exon 33 of 35	ENSP00000457428.1	D6RA96

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

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	0.093
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.2
DANN	Benign	0.91
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.47
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.092
Sift	Benign	0.043	D
Sift4G	Uncertain	0.025	D
Polyphen		0.0040	B
Vest4		0.22
MutPred		0.71		Loss of helix (P = 0.0033)
MVP		0.44
MPC		0.014
ClinPred		0.051	T
GERP RS		-1.3
PromoterAI		-0.0023	Neutral
Varity_R		0.11
gMVP		0.59
Mutation Taster		=96/4	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

hg19: chr20-62328152;