rs751160649

Variant names:

• chr19-54108382-C-A
• rs751160649
• NM_013342.4:c.367G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54108382-C-A
• chr19-54108382-C-G
• chr19-54108382-C-T

Variant summary

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

The NM_013342.4(TFPT):​c.367G>T​(p.Val123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TFPT NM_013342.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32720178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPT	NM_013342.4	c.367G>T	p.Val123Leu	missense_variant	Exon 4 of 6	ENST00000391759.6	NP_037474.1
TFPT	NM_001321792.2	c.340G>T	p.Val114Leu	missense_variant	Exon 4 of 6		NP_001308721.1
TFPT	XM_005278261.2	c.7G>T	p.Val3Leu	missense_variant	Exon 3 of 5		XP_005278318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPT	ENST00000391759.6	c.367G>T	p.Val123Leu	missense_variant	Exon 4 of 6	1	NM_013342.4	ENSP00000375639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.0098	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.058	T;T;T
Sift4G	Uncertain	0.052	T;T;D
Polyphen		0.98	D;.;.
Vest4		0.56
MutPred		0.23		Loss of MoRF binding (P = 0.0915);.;Loss of MoRF binding (P = 0.0915);
MVP		0.32
MPC		0.080
ClinPred		0.55	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.41

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: rs751160649; hg19: chr19-54611689;