rs3181195

Positions:

• chr9-114905862-C-A
• chr9-114905862-C-G
• chr9-114905862-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001244.4(TNFSF8):​c.276G>T​(p.Arg92Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF8 NM_001244.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

TNFSF8 (HGNC:11938): (TNF superfamily member 8) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF8/CD30, which is a cell surface antigen and a marker for Hodgkin lymphoma and related hematologic malignancies. The engagement of this cytokine expressed on B cell surface plays an inhibitory role in modulating Ig class switch. This cytokine was shown to enhance cell proliferation of some lymphoma cell lines, while to induce cell death and reduce cell proliferation of other lymphoma cell lines. The pleiotropic biologic activities of this cytokine on different CD30+ lymphoma cell lines may play a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

DELEC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04794994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF8	NM_001244.4	c.276G>T	p.Arg92Ser	missense_variant	3/4	ENST00000223795.3	NP_001235.1
TNFSF8	NM_001252290.1	c.276G>T	p.Arg92Ser	missense_variant	3/5		NP_001239219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF8	ENST00000223795.3	c.276G>T	p.Arg92Ser	missense_variant	3/4	1	NM_001244.4	ENSP00000223795.2
TNFSF8	ENST00000618336.4	c.276G>T	p.Arg92Ser	missense_variant	3/5	3		ENSP00000484651.1
DELEC1	ENST00000648852.1	n.50-15588C>A		intron_variant
DELEC1	ENST00000649565.1	n.225+20554C>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459762 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726340

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.9
DANN	Benign	0.96
DEOGEN2	Benign	0.093	T;D
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.017
Sift	Benign	0.24	.;T
Sift4G	Benign	0.35	T;T
Polyphen		0.013	.;B
Vest4		0.27
MutPred		0.33		Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);
MVP		0.043
MPC		0.26
ClinPred		0.091	T
GERP RS		1.7
Varity_R		0.14
gMVP		0.36

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

Other links and lift over

dbSNP: rs3181195; hg19: chr9-117668142;