16-11965340-G-C

Position:

• chr16-11965340-G-C

Variant summary

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

The NM_001192.3(TNFRSF17):​c.16G>C​(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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]

NPIPB2 (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=0.03666663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF17	NM_001192.3	c.16G>C	p.Gly6Arg	missense_variant	1/3	ENST00000053243.6	NP_001183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.16G>C	p.Gly6Arg	missense_variant	1/3	1	NM_001192.3	ENSP00000053243.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

TNFRSF17 NM_001192.2 exon 1 p.Gly6Arg (c.16G>C): This variant has not been reported in the literature and is not present in large control databases. This variant amino acid Arginine (Arg) is present in 6 primate species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.90	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	2.1	N;N
REVEL	Benign	0.044
Sift	Benign	0.66	T;T
Sift4G	Uncertain	0.035	D;D
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.22		Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);
MVP		0.095
MPC		0.0066
ClinPred		0.17	T
GERP RS		4.1
Varity_R		0.13
gMVP		0.23

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: rs2055184890; hg19: chr16-12059197;