16-3021963-T-C

Position:

• chr16-3021963-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016639.3(TNFRSF12A):​c.*137T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 933,164 control chromosomes in the GnomAD database, including 28,189 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3873 hom., cov: 33)
  • Exomes 𝑓: 0.24 (24316 hom.)
• Consequence: TNFRSF12A NM_016639.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

TNFRSF12A (HGNC:18152): (TNF receptor superfamily member 12A) Involved in positive regulation of extrinsic apoptotic signaling pathway and regulation of wound healing. Predicted to be located in cell surface and ruffle. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF12A	NM_016639.3	c.*137T>C		3_prime_UTR_variant	4/4	ENST00000326577.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF12A	ENST00000326577.9	c.*137T>C		3_prime_UTR_variant	4/4	1	NM_016639.3	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32106 AN: 152066 Hom.: 3871 Cov.: 33

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.257 AC: 21967 AN: 85356 Hom.: 3115 AF XY: 0.260 AC XY: 11633 AN XY: 44728

Gnomad AFR exome AF: 0.0983

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.243 AC: 189889 AN: 780980 Hom.: 24316 Cov.: 10 AF XY: 0.245 AC XY: 97489 AN XY: 397510

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.211 AC: 32113 AN: 152184 Hom.: 3873 Cov.: 33 AF XY: 0.215 AC XY: 16010 AN XY: 74392

Gnomad4 AFR AF: 0.0979

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.204

Alfa AF: 0.243 Hom.: 4194

Bravo AF: 0.207

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs13209; hg19: chr16-3071964; COSMIC: COSV50187617; COSMIC: COSV50187617;