19-54107096-T-C

Position:

• chr19-54107096-T-C

Variant summary

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

The NM_013342.4(TFPT):​c.716A>G​(p.Asp239Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TFPT NM_013342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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]

NDUFA3 (HGNC:7686): (NADH:ubiquinone oxidoreductase subunit A3) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. [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.716A>G	p.Asp239Gly	missense_variant	6/6	ENST00000391759.6
NDUFA3	NM_004542.4	c.*194T>C		3_prime_UTR_variant	4/4	ENST00000485876.6
TFPT	NM_001321792.2	c.689A>G	p.Asp230Gly	missense_variant	6/6
TFPT	XM_005278261.2	c.356A>G	p.Asp119Gly	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPT	ENST00000391759.6	c.716A>G	p.Asp239Gly	missense_variant	6/6	1	NM_013342.4	P1
NDUFA3	ENST00000485876.6	c.*194T>C		3_prime_UTR_variant	4/4	1	NM_004542.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jun 30, 2022

The c.716A>G (p.D239G) alteration is located in exon 6 (coding exon 6) of the TFPT gene. This alteration results from a A to G substitution at nucleotide position 716, causing the aspartic acid (D) at amino acid position 239 to be replaced by a glycine (G). 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	Benign	0.22
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.031
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.22	B;.
Vest4		0.67
MutPred		0.50		Gain of catalytic residue at G237 (P = 0.0636);.;
MVP		0.46
MPC		0.14
ClinPred		0.70	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.40

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: chr19-54610403;