16-11965427-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001192.3(TNFRSF17):​c.103C>G​(p.Leu35Val) 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. 16/22 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. L35I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFRSF17 NM_001192.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03305486).

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>G	p.Leu35Val	missense	Exon 1 of 3	NP_001183.2
	NPIPB2	NM_001395854.1		c.-536-1401G>C		intron	N/A	NP_001382783.1	A0A5F9ZI19
	NPIPB2	NM_001395855.1		c.-400-9190G>C		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>G	p.Leu35Val	missense	Exon 1 of 3	ENSP00000053243.1	Q02223-1
	TNFRSF17	ENST00000396495.3	TSL:1	c.103C>G	p.Leu35Val	missense	Exon 1 of 2	ENSP00000379753.3	Q02223-2
	TNFRSF17	ENST00000562385.1	TSL:1	c.76C>G	p.Leu26Val	missense	Exon 1 of 4	ENSP00000454314.1	H3BMB5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.59
DANN	Benign	0.72
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.67
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.016
Sift	Benign	0.89	T
Sift4G	Benign	0.89	T
Polyphen		0.012	B
Vest4		0.090
MVP		0.11
MPC		0.0071
ClinPred		0.055	T
GERP RS		-3.6
PromoterAI		-0.022	Neutral
Varity_R		0.081
gMVP		0.14

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

Other links and lift over

dbSNP: rs1274772306; hg19: chr16-12059284;