16-11965407-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001192.3(TNFRSF17):c.83G>A(p.Cys28Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

Genes affected

TNFRSF17 (HGNC:11913): (TNF receptor superfamily member 17) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [provided by RefSeq, Jul 2008]

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF17	NM_001192.3	c.83G>A	p.Cys28Tyr	missense_variant	1/3	ENST00000053243.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.83G>A	p.Cys28Tyr	missense_variant	1/3	1	NM_001192.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.83G>A (p.C28Y) alteration is located in exon 1 (coding exon 1) of the TNFRSF17 gene. This alteration results from a G to A substitution at nucleotide position 83, causing the cysteine (C) at amino acid position 28 to be replaced by a tyrosine (Y). 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	0.92
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-9.8	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.36
MutPred		0.95		Gain of glycosylation at P33 (P = 0.1315);Gain of glycosylation at P33 (P = 0.1315);
MVP		0.54
MPC		0.032
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.95
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-12059264;