chr16-11966306-A-T

Variant names:

• chr16-11966306-A-T
• rs373496
• NM_001192.3:c.242A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001192.3(TNFRSF17):​c.242A>T​(p.Asn81Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,726 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N81S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09325832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3	c.242A>T	p.Asn81Ile	missense_variant	Exon 2 of 3	ENST00000053243.6	NP_001183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6	c.242A>T	p.Asn81Ile	missense_variant	Exon 2 of 3	1	NM_001192.3	ENSP00000053243.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461726 Hom.: 0 Cov.: 44 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

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: 0.00000180

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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.7
DANN	Benign	0.95
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.056
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0040	B
Vest4		0.18
MutPred		0.28		Loss of disorder (P = 0.0287);
MVP		0.099
MPC		0.0085
ClinPred		0.18	T
GERP RS		-3.1
Varity_R		0.21
gMVP		0.21

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: rs373496; hg19: chr16-12060163;