rs162029

Variant summary

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

The NM_024091.4(FASTKD3):​c.1524+484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,984 control chromosomes in the GnomAD database, including 9,920 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 0.31 ( 9920 hom., cov: 32)

Consequence

FASTKD3
NM_024091.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

14 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]
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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

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=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FASTKD3NM_024091.4 linkc.1524+484C>T intron_variant Intron 3 of 6 ENST00000264669.10 NP_076996.2 Q14CZ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FASTKD3ENST00000264669.10 linkc.1524+484C>T intron_variant Intron 3 of 6 2 NM_024091.4 ENSP00000264669.5 Q14CZ7

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47444
AN:
151866
Hom.:
9888
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.567
Gnomad AMI
AF:
0.120
Gnomad AMR
AF:
0.396
Gnomad ASJ
AF:
0.211
Gnomad EAS
AF:
0.375
Gnomad SAS
AF:
0.197
Gnomad FIN
AF:
0.158
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.176
Gnomad OTH
AF:
0.290
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.313
AC:
47536
AN:
151984
Hom.:
9920
Cov.:
32
AF XY:
0.311
AC XY:
23094
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.567
AC:
23470
AN:
41402
American (AMR)
AF:
0.397
AC:
6064
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.211
AC:
732
AN:
3470
East Asian (EAS)
AF:
0.375
AC:
1930
AN:
5144
South Asian (SAS)
AF:
0.197
AC:
949
AN:
4822
European-Finnish (FIN)
AF:
0.158
AC:
1673
AN:
10588
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.176
AC:
11940
AN:
67970
Other (OTH)
AF:
0.290
AC:
611
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1422
2845
4267
5690
7112
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
426
852
1278
1704
2130
<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:
0.245
Hom.:
4659
Bravo
AF:
0.346
Asia WGS
AF:
0.298
AC:
1035
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.071
DANN
Benign
0.39
PhyloP100
-1.9
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs162029; hg19: chr5-7865527; API