Genetic Variant MTHFD1L:c.*205C>G (chr6-151101699-C-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.*205C>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 0.108 in 152,584 control chromosomes in the GnomAD database, including 1,146 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 0.11 ( 1145 hom., cov: 32)

Exomes 𝑓: 0.074 ( 1 hom. )

Consequence

MTHFD1L
NM_015440.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.150

Publications

11 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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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=-0.68).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 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
MTHFD1L	NM_015440.5	MANE Select	c.*205C>G	3_prime_UTR	Exon 28 of 28	NP_056255.2
MTHFD1L	NR_146719.2		n.3366C>G	non_coding_transcript_exon	Exon 29 of 29
MTHFD1L	NR_146720.2		n.4171C>G	non_coding_transcript_exon	Exon 29 of 29

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.*205C>G	3_prime_UTR	Exon 28 of 28	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	TSL:5	c.*205C>G	3_prime_UTR	Exon 28 of 28	ENSP00000478253.1
MTHFD1L	ENST00000618312.4	TSL:5	c.*205C>G	3_prime_UTR	Exon 28 of 28	ENSP00000479539.1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16413

AN:

152036

Hom.:

1140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0762

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.0812

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0701

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0744

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.0654

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:

0.0755

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.108

AC:

16427

AN:

152154

Hom.:

1145

Cov.:

AF XY:

0.113

AC XY:

8427

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.155

AC:

6436

AN:

41486

American (AMR)

AF:

0.0760

AC:

1162

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

437

AN:

3472

East Asian (EAS)

AF:

0.211

AC:

1094

AN:

5176

South Asian (SAS)

AF:

0.286

AC:

1376

AN:

4818

European-Finnish (FIN)

AF:

0.0812

AC:

859

AN:

10582

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0701

AC:

4764

AN:

68002

Other (OTH)

AF:

0.104

AC:

220

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

739

1478

2217

2956

3695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0298

Hom.:

Bravo

AF:

0.106

Asia WGS

AF:

0.227

AC:

787

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.15

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)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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