rs138676880

Variant names:

• chr13-23660489-C-A
• rs138676880
• NM_148957.4:c.735C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-23660489-C-A
• chr13-23660489-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_148957.4(TNFRSF19):​c.735C>A​(p.Cys245*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TNFRSF19 NM_148957.4 stop_gained, splice_region
• Scores: Splicing: ADA: 0.0002265
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF19	NM_148957.4	c.735C>A	p.Cys245*	stop_gained, splice_region_variant	Exon 7 of 10	ENST00000248484.9	NP_683760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF19	ENST00000248484.9	c.735C>A	p.Cys245*	stop_gained, splice_region_variant	Exon 7 of 10	1	NM_148957.4	ENSP00000248484.4
TNFRSF19	ENST00000382258.8	c.735C>A	p.Cys245*	stop_gained, splice_region_variant	Exon 7 of 9	1		ENSP00000371693.4
TNFRSF19	ENST00000382263.3	c.735C>A	p.Cys245*	stop_gained, splice_region_variant	Exon 7 of 10	1		ENSP00000371698.3
TNFRSF19	ENST00000403372.6	c.339C>A	p.Cys113*	stop_gained, splice_region_variant	Exon 5 of 8	2		ENSP00000385408.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459620 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726120

Gnomad4 AFR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.92
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.32
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

Other links and lift over

dbSNP: rs138676880; hg19: chr13-24234628;