rs17184211

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_024091.4(FASTKD3):c.1439-10T>A variant causes a 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. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.14 ( 1929 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27816 hom. )

Consequence

FASTKD3
NM_024091.4 intron

Scores

Splicing: ADA: 0.3709

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

methylcobalamin deficiency type cblE
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

MTRR 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=-0.8).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024091.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FASTKD3	NM_024091.4	MANE Select	c.1439-10T>A	intron	N/A	NP_076996.2
FASTKD3	NR_036553.2		n.54-10T>A	intron	N/A
FASTKD3	NR_073608.2		n.54-10T>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FASTKD3	ENST00000264669.10	TSL:2 MANE Select	c.1439-10T>A	intron	N/A	ENSP00000264669.5	Q14CZ7
FASTKD3	ENST00000282110.8	TSL:1	n.33-10T>A	intron	N/A
FASTKD3	ENST00000507036.1	TSL:1	n.1439-10T>A	intron	N/A	ENSP00000421798.1	D6RAR6

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

GnomAD2 exomes

AF:

0.143

AC:

36031

AN:

251214

AF XY:

0.146

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 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

African (AFR)

AF:

0.0514

AC:

1717

AN:

33418

American (AMR)

AF:

0.0726

AC:

3245

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4757

AN:

26098

East Asian (EAS)

AF:

0.000454

AC:

AN:

39666

South Asian (SAS)

AF:

0.0913

AC:

7862

AN:

86150

European-Finnish (FIN)

AF:

0.184

AC:

9851

AN:

53394

Middle Eastern (MID)

AF:

0.105

AC:

603

AN:

5758

European-Non Finnish (NFE)

AF:

0.210

AC:

232994

AN:

1107384

Other (OTH)

AF:

0.167

AC:

10072

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9556

19112

28668

38224

47780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7768

15536

23304

31072

38840

<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:

0.143

AC:

21618

AN:

150840

Hom.:

1929

Cov.:

AF XY:

0.141

AC XY:

10356

AN XY:

73570

show subpopulations

African (AFR)

AF:

0.0578

AC:

2398

AN:

41480

American (AMR)

AF:

0.107

AC:

1621

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3464

East Asian (EAS)

AF:

0.00137

AC:

AN:

5110

South Asian (SAS)

AF:

0.0891

AC:

407

AN:

4570

European-Finnish (FIN)

AF:

0.193

AC:

1993

AN:

10336

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14052

AN:

67486

Other (OTH)

AF:

0.116

AC:

241

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

900

1801

2701

3602

4502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.131

Hom.:

303

Bravo

AF:

0.131

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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