Genetic Variant MTHFR:c.*4075_*4077delAAA (chr1-11786602-ATTT-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005957.5(MTHFR):c.*4075_*4077delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 37 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MTHFR
NM_005957.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

3 publications found

Variant links:

Genes affected

MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

MTHFR links:

C1orf167 (HGNC:25262): (chromosome 1 open reading frame 167) Implicated in coronary artery disease. [provided by Alliance of Genome Resources, Apr 2022]

C1orf167 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005957.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFR	NM_005957.5	MANE Select	c.4075_4077delAAA	3_prime_UTR	Exon 12 of 12	NP_005948.3
C1orf167	NM_001010881.2	MANE Select	c.3568-769_3568-767delTTT	intron	N/A	NP_001010881.1	Q5SNV9-1
MTHFR	NM_001330358.2		c.4075_4077delAAA	3_prime_UTR	Exon 12 of 12	NP_001317287.1	P42898-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTHFR	ENST00000376590.9	TSL:1 MANE Select	c.4075_4077delAAA	3_prime_UTR	Exon 12 of 12	ENSP00000365775.3	P42898-1
MTHFR	ENST00000376592.6	TSL:1	c.4075_4077delAAA	3_prime_UTR	Exon 12 of 12	ENSP00000365777.1	P42898-1
C1orf167	ENST00000688073.1	MANE Select	c.3568-769_3568-767delTTT	intron	N/A	ENSP00000510540.1	Q5SNV9-1

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2238

AN:

142082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00933

Gnomad AMI

AF:

0.00226

Gnomad AMR

AF:

0.00887

Gnomad ASJ

AF:

0.00356

Gnomad EAS

AF:

0.0111

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0101

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0108

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0158

AC:

2240

AN:

142110

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1095

AN XY:

68388

show subpopulations

African (AFR)

AF:

0.00937

AC:

362

AN:

38644

American (AMR)

AF:

0.00886

AC:

127

AN:

14326

Ashkenazi Jewish (ASJ)

AF:

0.00356

AC:

AN:

3370

East Asian (EAS)

AF:

0.0111

AC:

AN:

4770

South Asian (SAS)

AF:

0.0242

AC:

106

AN:

4376

European-Finnish (FIN)

AF:

0.0316

AC:

252

AN:

7984

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0199

AC:

1302

AN:

65514

Other (OTH)

AF:

0.0107

AC:

AN:

1966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

193

289

386

482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0272

Hom.:

551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism

(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

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