chr13-23660470-G-A

Position:

chr13-23660470-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_148957.4(TNFRSF19):c.716G>A(p.Arg239His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TNFRSF19
NM_148957.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.543

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09786257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF19	NM_148957.4 linkuse as main transcript	c.716G>A	p.Arg239His	missense_variant	7/10	ENST00000248484.9	NP_683760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF19	ENST00000248484.9 linkuse as main transcript	c.716G>A	p.Arg239His	missense_variant	7/10	1	NM_148957.4	ENSP00000248484	P1	Q9NS68-2
TNFRSF19	ENST00000382258.8 linkuse as main transcript	c.716G>A	p.Arg239His	missense_variant	7/9	1		ENSP00000371693		Q9NS68-1
TNFRSF19	ENST00000382263.3 linkuse as main transcript	c.716G>A	p.Arg239His	missense_variant	7/10	1		ENSP00000371698	P1	Q9NS68-2
TNFRSF19	ENST00000403372.6 linkuse as main transcript	c.320G>A	p.Arg107His	missense_variant	5/8	2		ENSP00000385408		Q9NS68-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251186

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461108

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

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 18, 2022

The c.716G>A (p.R239H) alteration is located in exon 7 (coding exon 6) of the TNFRSF19 gene. This alteration results from a G to A substitution at nucleotide position 716, causing the arginine (R) at amino acid position 239 to be replaced by a histidine (H). 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

Benign

0.077

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;.;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.098

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.27

B;.;B;B

Vest4

0.23

MutPred

0.44

Gain of catalytic residue at V242 (P = 2e-04);.;Gain of catalytic residue at V242 (P = 2e-04);Gain of catalytic residue at V242 (P = 2e-04);

MVP

0.18

MPC

0.29

ClinPred

0.15

GERP RS

-0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.28

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

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