dbSNP rs254262: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TFPT	NM_013342.4 link	c.353+730C>T	intron_variant	Intron 3 of 5	ENST00000391759.6	NP_037474.1
TFPT	NM_001321792.2 link	c.326+730C>T	intron_variant	Intron 3 of 5		NP_001308721.1
TFPT	XM_005278261.2 link	c.-8+730C>T	intron_variant	Intron 2 of 4		XP_005278318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPT	ENST00000391759.6 link	c.353+730C>T		intron_variant	Intron 3 of 5	1	NM_013342.4	ENSP00000375639.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over