19-54114448-G-T

Variant names:

• chr19-54114448-G-T
• NM_013342.4:c.276C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_013342.4(TFPT):​c.276C>A​(p.Ile92Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TFPT NM_013342.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.247 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPT	NM_013342.4	c.276C>A	p.Ile92Ile	synonymous_variant	Exon 2 of 6	ENST00000391759.6	NP_037474.1
TFPT	NM_001321792.2	c.249C>A	p.Ile83Ile	synonymous_variant	Exon 2 of 6		NP_001308721.1
TFPT	XM_005278261.2	c.-89C>A		5_prime_UTR_variant	Exon 1 of 5		XP_005278318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPT	ENST00000391759.6	c.276C>A	p.Ile92Ile	synonymous_variant	Exon 2 of 6	1	NM_013342.4	ENSP00000375639.1
TFPT	ENST00000391758.5	c.249C>A	p.Ile83Ile	synonymous_variant	Exon 2 of 6	1		ENSP00000375638.1
TFPT	ENST00000391757.1	c.276C>A	p.Ile92Ile	synonymous_variant	Exon 2 of 6	5		ENSP00000375637.1
TFPT	ENST00000420715.6	n.276C>A		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000395180.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460418 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726366

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: 9.00e-7

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
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54617828;