chr16-3021963-T-C

Variant names:

• chr16-3021963-T-C
• rs13209
• NM_016639.3:c.*137T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016639.3. 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
	TNFRSF12A	NM_016639.3	MANE Select	c.*137T>C		3_prime_UTR	Exon 4 of 4	NP_057723.1	Q9NP84-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF12A	ENST00000326577.9	TSL:1 MANE Select	c.*137T>C		3_prime_UTR	Exon 4 of 4	ENSP00000326737.5	Q9NP84-1
	TNFRSF12A	ENST00000341627.5	TSL:1	c.*137T>C		3_prime_UTR	Exon 3 of 3	ENSP00000343894.5	Q9NP84-2
	TNFRSF12A	ENST00000575124.1	TSL:2	c.*9T>C		3_prime_UTR	Exon 3 of 3	ENSP00000460610.1	I3L3P4

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

GnomAD2 exomes AF: 0.257 AC: 21967 AN: 85356 AF XY: 0.260

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 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

African (AFR) AF: 0.0907 AC: 1719 AN: 18962

American (AMR) AF: 0.379 AC: 9174 AN: 24204

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 3196 AN: 16594

East Asian (EAS) AF: 0.124 AC: 4044 AN: 32598

South Asian (SAS) AF: 0.292 AC: 16799 AN: 57484

European-Finnish (FIN) AF: 0.291 AC: 9145 AN: 31452

Middle Eastern (MID) AF: 0.199 AC: 572 AN: 2868

European-Non Finnish (NFE) AF: 0.244 AC: 136805 AN: 559806

Other (OTH) AF: 0.228 AC: 8435 AN: 37012

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

African (AFR) AF: 0.0979 AC: 4068 AN: 41542

American (AMR) AF: 0.292 AC: 4471 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3470

East Asian (EAS) AF: 0.119 AC: 617 AN: 5180

South Asian (SAS) AF: 0.288 AC: 1391 AN: 4824

European-Finnish (FIN) AF: 0.295 AC: 3131 AN: 10596

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17080 AN: 67960

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.240 Hom.: 5295

Bravo AF: 0.207

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.58
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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