dbSNP rs200497052: TFPT:p.Arg197Gln (chr19-54108078-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013342.4(TFPT):c.590G>A(p.Arg197Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,557,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TFPT
NM_013342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0467799).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPT	NM_013342.4	MANE Select	c.590G>A	p.Arg197Gln	missense	Exon 5 of 6	NP_037474.1	P0C1Z6-1
	TFPT	NM_001321792.2		c.563G>A	p.Arg188Gln	missense	Exon 5 of 6	NP_001308721.1	P0C1Z6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFPT	ENST00000391759.6	TSL:1 MANE Select	c.590G>A	p.Arg197Gln	missense	Exon 5 of 6	ENSP00000375639.1	P0C1Z6-1
TFPT	ENST00000391758.5	TSL:1	c.563G>A	p.Arg188Gln	missense	Exon 5 of 6	ENSP00000375638.1	P0C1Z6-2
TFPT	ENST00000911296.1		c.641G>A	p.Arg214Gln	missense	Exon 5 of 6	ENSP00000581355.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

206042

AF XY:

0.000145

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

159

AN:

1405270

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

693680

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31586

American (AMR)

AF:

0.000166

AC:

AN:

36200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21970

East Asian (EAS)

AF:

0.00

AC:

AN:

39222

South Asian (SAS)

AF:

0.0000514

AC:

AN:

77760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.000131

AC:

142

AN:

1084082

Other (OTH)

AF:

0.0000866

AC:

AN:

57750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000854

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000908

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.33

M_CAP

Benign

0.057

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.95

PhyloP100

3.9

PROVEAN

Benign

2.1

REVEL

Benign

0.070

Sift

Pathogenic

0.0

Vest4

0.44

MutPred

0.19

Gain of MoRF binding (P = 0.0545)

MVP

0.47

ClinPred

0.12

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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