Variant chr13-23615874-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_148957.4(TNFRSF19):c.188G>T(p.Gly63Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TNFRSF19
NM_148957.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.58

Variant links:

Genes affected

TNFRSF19 (HGNC:11915): (TNF receptor superfamily member 19) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is highly expressed during embryonic development. It has been shown to interact with TRAF family members, and to activate JNK signaling pathway when overexpressed in cells. This receptor is capable of inducing apoptosis by a caspase-independent mechanism, and it is thought to play an essential role in embryonic development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

TNFRSF19 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF19	NM_148957.4 link	c.188G>T	p.Gly63Val	missense_variant	4/10	ENST00000248484.9	NP_683760.1	Q9NS68-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFRSF19	ENST00000248484.9 link	c.188G>T	p.Gly63Val	missense_variant	4/10	1	NM_148957.4	ENSP00000248484.4	Q9NS68-2
TNFRSF19	ENST00000382258.8 link	c.188G>T	p.Gly63Val	missense_variant	4/9	1		ENSP00000371693.4	Q9NS68-1
TNFRSF19	ENST00000382263.3 link	c.188G>T	p.Gly63Val	missense_variant	4/10	1		ENSP00000371698.3	Q9NS68-2
TNFRSF19	ENST00000403372 link	c.-209G>T		5_prime_UTR_variant	2/8	2		ENSP00000385408.2	Q9NS68-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244578

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000908

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000689

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.188G>T (p.G63V) alteration is located in exon 4 (coding exon 3) of the TNFRSF19 gene. This alteration results from a G to T substitution at nucleotide position 188, causing the glycine (G) at amino acid position 63 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

.;D;.

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.4

M;M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.9

D;D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.87

MutPred

0.48

Gain of catalytic residue at K60 (P = 0.021);Gain of catalytic residue at K60 (P = 0.021);Gain of catalytic residue at K60 (P = 0.021);

MVP

0.62

MPC

0.54

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.99

gMVP

0.92

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over