22-41926712-G-T

Position:

• chr22-41926712-G-T

Variant summary

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

The NM_052945.4(TNFRSF13C):​c.62C>A​(p.Pro21Gln) 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. 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. P21R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFRSF13C NM_052945.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

Genes affected

TNFRSF13C (HGNC:17755): (TNF receptor superfamily member 13C) B cell-activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. Overexpression of Baff in mice results in mature B-cell hyperplasia and symptoms of systemic lupus erythematosus (SLE). Also, some SLE patients have increased levels of BAFF in serum. Therefore, it has been proposed that abnormally high levels of BAFF may contribute to the pathogenesis of autoimmune diseases by enhancing the survival of autoreactive B cells. The protein encoded by this gene is a receptor for BAFF and is a type III transmembrane protein containing a single extracellular cysteine-rich domain. It is thought that this receptor is the principal receptor required for BAFF-mediated mature B-cell survival. [provided by RefSeq, Jul 2008]

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=0.04172349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF13C	NM_052945.4	c.62C>A	p.Pro21Gln	missense_variant	1/3	ENST00000291232.5	NP_443177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13C	ENST00000291232.5	c.62C>A	p.Pro21Gln	missense_variant	1/3	1	NM_052945.4	ENSP00000291232.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1297242 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 638296

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.82
DEOGEN2	Benign	0.096	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.93	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	0.72	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.42		Loss of loop (P = 0.0389);
MVP		0.043
MPC		0.76
ClinPred		0.065	T
GERP RS		0.12
Varity_R		0.073
gMVP		0.046

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: rs77874543; hg19: chr22-42322716;