rs254262

Positions:

• chr19-54109321-G-A
• chr19-54109321-G-T

Variant summary

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

The NM_013342.4(TFPT):​c.353+730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,830 control chromosomes in the GnomAD database, including 5,923 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 0.28 (5889 hom., cov: 32)
  • Exomes 𝑓: 0.28 (34 hom.)
• Consequence: TFPT NM_013342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

Genes affected

TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPT	NM_013342.4	c.353+730C>T		intron_variant		ENST00000391759.6	NP_037474.1
TFPT	NM_001321792.2	c.326+730C>T		intron_variant			NP_001308721.1
TFPT	XM_005278261.2	c.-8+730C>T		intron_variant			XP_005278318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPT	ENST00000391759.6	c.353+730C>T		intron_variant		1	NM_013342.4	ENSP00000375639.1
TFPT	ENST00000391758.5	c.326+730C>T		intron_variant		1		ENSP00000375638.1
TFPT	ENST00000391757.1	c.353+730C>T		intron_variant		5		ENSP00000375637.1
TFPT	ENST00000420715.6	n.283-926C>T		intron_variant		5		ENSP00000395180.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41779 AN: 151950 Hom.: 5867 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.276 AC: 210 AN: 760 Hom.: 34 AF XY: 0.263 AC XY: 133 AN XY: 506

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.275 AC: 41845 AN: 152070 Hom.: 5889 Cov.: 32 AF XY: 0.279 AC XY: 20717 AN XY: 74336

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.299

Alfa AF: 0.249 Hom.: 4778

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs254262; hg19: chr19-54612628;