dbSNP rs1261654402: TNFRSF6B:p.Leu12Met (chr20-63696801-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003823.4(TNFRSF6B):c.34C>A(p.Leu12Met) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L12V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNFRSF6B
NM_003823.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

0 publications found

Variant links:

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]

TNFRSF6B links:

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]

RTEL1-TNFRSF6B links:

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ACMG classification

Classification was made for transcript

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=0.22802407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF6B	NM_003823.4 link	c.34C>A	p.Leu12Met	missense_variant	Exon 1 of 3	ENST00000369996.3	NP_003814.1	O95407
RTEL1-TNFRSF6B	NR_037882.1 link	n.4768C>A		non_coding_transcript_exon_variant	Exon 36 of 38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNFRSF6B	ENST00000369996.3 link	c.34C>A	p.Leu12Met	missense_variant	Exon 1 of 3	1	NM_003823.4	ENSP00000359013.1	O95407
RTEL1-TNFRSF6B	ENST00000492259.6 link	n.*1373C>A		non_coding_transcript_exon_variant	Exon 33 of 35	5		ENSP00000457428.1	D6RA96
RTEL1-TNFRSF6B	ENST00000492259.6 link	n.*1373C>A		3_prime_UTR_variant	Exon 33 of 35	5		ENSP00000457428.1	D6RA96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722810

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.00

AC:

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.00

AC:

AN:

85274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108938

Other (OTH)

AF:

0.00

AC:

AN:

59954

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.6

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.11

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.78

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.30

M_CAP

Benign

0.048

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.2

PhyloP100

-0.098

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.070

REVEL

Benign

0.15

Sift

Benign

0.079

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.23

MutPred

0.52

Loss of helix (P = 0.0033);

MVP

0.17

MPC

0.014

ClinPred

0.13

GERP RS

-0.58

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.13

gMVP

0.41

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over