19-54110098-C-G

Position:

• chr19-54110098-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013342.4(TFPT):​c.306G>C​(p.Arg102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFPT NM_013342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPT	NM_013342.4	c.306G>C	p.Arg102Ser	missense_variant	3/6	ENST00000391759.6
TFPT	NM_001321792.2	c.279G>C	p.Arg93Ser	missense_variant	3/6
TFPT	XM_005278261.2	c.-55G>C		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPT	ENST00000391759.6	c.306G>C	p.Arg102Ser	missense_variant	3/6	1	NM_013342.4	P1
TFPT	ENST00000391758.5	c.279G>C	p.Arg93Ser	missense_variant	3/6	1
TFPT	ENST00000391757.1	c.306G>C	p.Arg102Ser	missense_variant	3/6	5
TFPT	ENST00000420715.6	c.283-1703G>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.306G>C (p.R102S) alteration is located in exon 3 (coding exon 3) of the TFPT gene. This alteration results from a G to C substitution at nucleotide position 306, causing the arginine (R) at amino acid position 102 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.1	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.29	B;.;.
Vest4		0.89
MutPred		0.53		Loss of catalytic residue at R102 (P = 0.085);.;Loss of catalytic residue at R102 (P = 0.085);
MVP		0.47
MPC		0.11
ClinPred		0.99	D
GERP RS		0.96
Varity_R		0.87
gMVP		0.71

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: chr19-54613481;