Genetic Variant NM_003823.4:c.19C>A (chr20-63696786-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.19C>A(p.Pro7Thr) 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 (★).

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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.316

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=0.08444014).

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.19C>A	p.Pro7Thr	missense	Exon 1 of 3	NP_003814.1	O95407
	RTEL1-TNFRSF6B	NR_037882.1		n.4753C>A		non_coding_transcript_exon	Exon 36 of 38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF6B	ENST00000369996.3	TSL:1 MANE Select	c.19C>A	p.Pro7Thr	missense	Exon 1 of 3	ENSP00000359013.1	O95407
RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1358C>A		non_coding_transcript_exon	Exon 33 of 35	ENSP00000457428.1	D6RA96
RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1358C>A		3_prime_UTR	Exon 33 of 35	ENSP00000457428.1	D6RA96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719436

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

43926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25308

East Asian (EAS)

AF:

0.00

AC:

AN:

39498

South Asian (SAS)

AF:

0.00

AC:

AN:

84118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105994

Other (OTH)

AF:

0.00

AC:

AN:

59752

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.8

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.079

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.47

M_CAP

Benign

0.018

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

-0.32

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.31

REVEL

Benign

0.094

Sift

Benign

0.046

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.065

MutPred

0.44

Gain of helix (P = 0.0325)

MVP

0.21

MPC

0.014

ClinPred

0.069

GERP RS

-0.73

PromoterAI

0.0059

Neutral

(source)

Varity_R

0.034

gMVP

0.52

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over