Genetic Variant TFPT:c.353+730C>T (chr19-54109321-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013342.4(TFPT):c.353+730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,830 control chromosomes in the GnomAD database, including 5,923 homozygotes. 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: 𝑓 0.28 ( 5889 hom., cov: 32)

Exomes 𝑓: 0.28 ( 34 hom. )

Consequence

TFPT
NM_013342.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

34 publications found

Variant links:

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]

TFPT links:

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]

NDUFA3 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

NDUFA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013342.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPT	NM_013342.4	MANE Select	c.353+730C>T		intron	N/A	NP_037474.1
	TFPT	NM_001321792.2		c.326+730C>T		intron	N/A	NP_001308721.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TFPT	ENST00000391759.6	TSL:1 MANE Select	c.353+730C>T	intron	N/A	ENSP00000375639.1
TFPT	ENST00000391758.5	TSL:1	c.326+730C>T	intron	N/A	ENSP00000375638.1
TFPT	ENST00000391757.1	TSL:5	c.353+730C>T	intron	N/A	ENSP00000375637.1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41779

AN:

151950

Hom.:

5867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.276

AC:

210

AN:

760

Hom.:

AF XY:

0.263

AC XY:

133

AN XY:

506

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.548

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.346

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.252

AC:

156

AN:

618

Other (OTH)

AF:

0.318

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

41845

AN:

152070

Hom.:

5889

Cov.:

AF XY:

0.279

AC XY:

20717

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.284

AC:

11789

AN:

41474

American (AMR)

AF:

0.358

AC:

5466

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1077

AN:

3470

East Asian (EAS)

AF:

0.349

AC:

1801

AN:

5166

South Asian (SAS)

AF:

0.326

AC:

1570

AN:

4818

European-Finnish (FIN)

AF:

0.273

AC:

2891

AN:

10582

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16342

AN:

67960

Other (OTH)

AF:

0.299

AC:

632

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1563

3126

4688

6251

7814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.254

Hom.:

8833

Bravo

AF:

0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

PhyloP100

0.027

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over