Variant 5-7865993-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024091.4(FASTKD3):c.1439-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,607,630 control chromosomes in the GnomAD database, including 29,745 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 0.14 ( 1929 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27816 hom. )

Consequence

FASTKD3
NM_024091.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.3709

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314

Variant links:

Genes affected

FASTKD3 (HGNC:28758): (FAST kinase domains 3) This gene encodes a member of a small family of Fas-activated serine/threonine kinase domain (FASTKD) containing proteins that share an amino terminal mitochondrial targeting domain and multiple carboxy terminal FAST domains as well as a putative RNA-binding RAP domain. The members of this family are ubiquitously expressed and are generally most abundant in mitochondria-enriched tissues such as heart, skeletal muscle and brown-adipose tissue. Some members of this protein family may play a role in apoptosis. The protein encoded by this gene interacts with components of the mitochondrial respiratory and translation networks. A pseudogene of this gene is also present on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

FASTKD3 links:

MTRR (HGNC:7473): (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MTRR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTKD3	NM_024091.4 linkuse as main transcript	c.1439-10T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264669.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTKD3	ENST00000264669.10 linkuse as main transcript	c.1439-10T>A		splice_polypyrimidine_tract_variant, intron_variant		2	NM_024091.4	P1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21599

AN:

150722

Hom.:

1926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.00137

Gnomad SAS

AF:

0.0885

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.143

AC:

36031

AN:

251214

Hom.:

3288

AF XY:

0.146

AC XY:

19821

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0876

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.186

AC:

271119

AN:

1456790

Hom.:

27816

Cov.:

AF XY:

0.184

AC XY:

133542

AN XY:

725054

show subpopulations

Gnomad4 AFR exome

AF:

0.0514

Gnomad4 AMR exome

AF:

0.0726

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.0913

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.143

AC:

21618

AN:

150840

Hom.:

1929

Cov.:

AF XY:

0.141

AC XY:

10356

AN XY:

73570

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.00137

Gnomad4 SAS

AF:

0.0891

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.131

Hom.:

303

Bravo

AF:

0.131

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.37

dbscSNV1_RF

Benign

0.64

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.41

Position offset: -10

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over