16-11965427-C-A

Variant names:

• chr16-11965427-C-A
• rs1274772306
• NM_001192.3:c.103C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001192.3(TNFRSF17):​c.103C>A​(p.Leu35Ile) 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 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: -0.670
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09626362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001192.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF17	NM_001192.3	MANE Select	c.103C>A	p.Leu35Ile	missense	Exon 1 of 3	NP_001183.2
	NPIPB2	NM_001395854.1		c.-536-1401G>T		intron	N/A	NP_001382783.1	A0A5F9ZI19
	NPIPB2	NM_001395855.1		c.-400-9190G>T		intron	N/A	NP_001382784.1	A0A5F9ZI19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF17	ENST00000053243.6	TSL:1 MANE Select	c.103C>A	p.Leu35Ile	missense	Exon 1 of 3	ENSP00000053243.1	Q02223-1
	TNFRSF17	ENST00000396495.3	TSL:1	c.103C>A	p.Leu35Ile	missense	Exon 1 of 2	ENSP00000379753.3	Q02223-2
	TNFRSF17	ENST00000562385.1	TSL:1	c.76C>A	p.Leu26Ile	missense	Exon 1 of 4	ENSP00000454314.1	H3BMB5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.3
DANN	Benign	0.89
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.67
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.088
Sift	Benign	0.25	T
Sift4G	Benign	0.31	T
Polyphen		0.67	P
Vest4		0.18
MutPred		0.56		Loss of glycosylation at P34 (P = 0.0817)
MVP		0.12
MPC		0.0069
ClinPred		0.83	D
GERP RS		-3.6
PromoterAI		-0.038	Neutral
Varity_R		0.18
gMVP		0.090
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1274772306; hg19: chr16-12059284;