rs6997

Positions:

• chr3-49416401-C-T

Variant summary

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

The ENST00000273590.4(TCTA):​c.*1539C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 261,562 control chromosomes in the GnomAD database, including 11,879 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 0.30 (7228 hom., cov: 32)
  • Exomes 𝑓: 0.27 (4651 hom.)
• Consequence: TCTA ENST00000273590.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

Genes affected

TCTA (HGNC:11692): (T cell leukemia translocation altered) Involved in negative regulation of osteoclast differentiation and osteoclast fusion. Predicted to be integral component of 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTA	NM_022171.3	c.*1539C>T		3_prime_UTR_variant	3/3	ENST00000273590.4	NP_071503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTA	ENST00000273590.4	c.*1539C>T		3_prime_UTR_variant	3/3	1	NM_022171.3	ENSP00000273590	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45243 AN: 152072 Hom.: 7220 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.273 AC: 29831 AN: 109372 Hom.: 4651 Cov.: 0 AF XY: 0.267 AC XY: 15568 AN XY: 58336

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.0504

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.297 AC: 45274 AN: 152190 Hom.: 7228 Cov.: 32 AF XY: 0.300 AC XY: 22285 AN XY: 74400

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.0589

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.298

Alfa AF: 0.300 Hom.: 7317

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.62

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: rs6997; hg19: chr3-49453834;