Genetic Variant MTHFD1L:c.*120A>G (chr6-151101614-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015440.5(MTHFD1L):c.*120A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,540 control chromosomes in the GnomAD database, including 4,149 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 0.22 ( 4129 hom., cov: 32)

Exomes 𝑓: 0.27 ( 20 hom. )

Consequence

MTHFD1L
NM_015440.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.522

Publications

10 publications found

Variant links:

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]

MTHFD1L links:

ENSG00000223598 (HGNC:):

ENSG00000223598 links:

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new If you want to explore the variant's impact on the transcript NM_015440.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFD1L	NM_015440.5	MANE Select	c.*120A>G	3_prime_UTR	Exon 28 of 28	NP_056255.2
MTHFD1L	NM_001242767.2		c.*120A>G	3_prime_UTR	Exon 28 of 28	NP_001229696.1	B7ZM99
MTHFD1L	NM_001242768.2		c.*120A>G	3_prime_UTR	Exon 28 of 28	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.*120A>G	3_prime_UTR	Exon 28 of 28	ENSP00000356290.3	Q6UB35-1
MTHFD1L	ENST00000611279.4	TSL:5	c.*120A>G	3_prime_UTR	Exon 28 of 28	ENSP00000478253.1	B7ZM99
MTHFD1L	ENST00000939695.1		c.*120A>G	3_prime_UTR	Exon 28 of 28	ENSP00000609754.1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34187

AN:

151990

Hom.:

4124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.0887

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.273

AC:

118

AN:

432

Hom.:

Cov.:

AF XY:

0.273

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.272

AC:

116

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.225

AC:

34201

AN:

152108

Hom.:

4129

Cov.:

AF XY:

0.224

AC XY:

16671

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.142

AC:

5895

AN:

41512

American (AMR)

AF:

0.232

AC:

3541

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3466

East Asian (EAS)

AF:

0.0883

AC:

457

AN:

5176

South Asian (SAS)

AF:

0.229

AC:

1105

AN:

4820

European-Finnish (FIN)

AF:

0.276

AC:

2915

AN:

10548

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18667

AN:

67992

Other (OTH)

AF:

0.229

AC:

484

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1336

2672

4008

5344

6680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.262

Hom.:

7098

Bravo

AF:

0.215

Asia WGS

AF:

0.151

AC:

525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.5

(source)

DANN

Benign

0.59

PhyloP100

0.52

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

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over