6-150882864-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015440.5(MTHFD1L):āc.520A>Gā(p.Lys174Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000604 in 1,573,550 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.000065 ( 0 hom. )
Consequence
MTHFD1L
NM_015440.5 missense
NM_015440.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30448747).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTHFD1L | NM_015440.5 | c.520A>G | p.Lys174Glu | missense_variant | 5/28 | ENST00000367321.8 | NP_056255.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTHFD1L | ENST00000367321.8 | c.520A>G | p.Lys174Glu | missense_variant | 5/28 | 1 | NM_015440.5 | ENSP00000356290.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000190 AC: 4AN: 210380Hom.: 0 AF XY: 0.00000872 AC XY: 1AN XY: 114692
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GnomAD4 exome AF: 0.0000647 AC: 92AN: 1421346Hom.: 0 Cov.: 30 AF XY: 0.0000609 AC XY: 43AN XY: 706110
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 24, 2024 | The c.520A>G (p.K174E) alteration is located in exon 5 (coding exon 5) of the MTHFD1L gene. This alteration results from a A to G substitution at nucleotide position 520, causing the lysine (K) at amino acid position 174 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;N
REVEL
Benign
Sift
Benign
T;.;T;.;T
Sift4G
Benign
T;T;D;T;T
Polyphen
P;P;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at