chr6-150926146-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015440.5(MTHFD1L):āc.1107A>Cā(p.Gln369His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000021 ( 0 hom. )
Consequence
MTHFD1L
NM_015440.5 missense
NM_015440.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 0.316
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10389522).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFD1L | NM_015440.5 | c.1107A>C | p.Gln369His | missense_variant | 11/28 | ENST00000367321.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFD1L | ENST00000367321.8 | c.1107A>C | p.Gln369His | missense_variant | 11/28 | 1 | NM_015440.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251258Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135790
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461548Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727028
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74460
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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 | Sep 01, 2021 | The c.1110A>C (p.Q370H) alteration is located in exon 11 (coding exon 11) of the MTHFD1L gene. This alteration results from a A to C substitution at nucleotide position 1110, causing the glutamine (Q) at amino acid position 370 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of helix (P = 0.0558);.;.;
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