chr19-54114455-C-A

Variant names:

• chr19-54114455-C-A
• rs781740615
• NM_013342.4:c.269G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013342.4(TFPT):​c.269G>T​(p.Arg90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,716 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: 0.0000055 (0 hom.)
• Consequence: TFPT NM_013342.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3849237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPT	NM_013342.4	c.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 6	ENST00000391759.6	NP_037474.1
TFPT	XM_005278261.2	c.-96G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		XP_005278318.1
TFPT	NM_001321792.2	c.242G>T	p.Arg81Leu	missense_variant	Exon 2 of 6		NP_001308721.1
TFPT	XM_005278261.2	c.-96G>T		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.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 6	1	NM_013342.4	ENSP00000375639.1
TFPT	ENST00000391758.5	c.242G>T	p.Arg81Leu	missense_variant	Exon 2 of 6	1		ENSP00000375638.1
TFPT	ENST00000391757.1	c.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 6	5		ENSP00000375637.1
TFPT	ENST00000420715.6	n.269G>T		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000395180.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249354 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460716 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 726538

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.57
MutPred		0.29		Gain of catalytic residue at R90 (P = 0.0016);.;Gain of catalytic residue at R90 (P = 0.0016);
MVP		0.51
MPC		0.27
ClinPred		0.89	D
GERP RS		4.9
Varity_R		0.27
gMVP		0.54

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: rs781740615; hg19: chr19-54617835;