Variant chr15-79845218-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006441.4(MTHFS):c.604A>G(p.Thr202Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,614,148 control chromosomes in the GnomAD database, including 6,373 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.075 ( 478 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5895 hom. )

Consequence

MTHFS
NM_006441.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.55

Variant links:

Genes affected

MTHFS (HGNC:7437): (methenyltetrahydrofolate synthetase) The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MTHFS links:

ST20-MTHFS (HGNC:):

ST20-MTHFS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017362237).

BP6

Variant 15-79845218-T-C is Benign according to our data. Variant chr15-79845218-T-C is described in ClinVar as [Benign]. Clinvar id is 2038284.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTHFS	NM_006441.4 linkuse as main transcript	c.604A>G	p.Thr202Ala	missense_variant	3/3	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2 linkuse as main transcript	c.532A>G	p.Thr178Ala	missense_variant	4/4		NP_001186689.1
MTHFS	NM_001199758.1 linkuse as main transcript	c.433A>G	p.Thr145Ala	missense_variant	3/3		NP_001186687.1
MTHFS	NR_037654.2 linkuse as main transcript	n.711A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000258874.4 linkuse as main transcript	c.604A>G	p.Thr202Ala	missense_variant	3/3	1	NM_006441.4	ENSP00000258874	P1	P49914-1
MTHFS	ENST00000559722.2 linkuse as main transcript	c.691A>G	p.Thr231Ala	missense_variant	3/3	2		ENSP00000489076
MTHFS	ENST00000560261.1 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant, NMD_transcript_variant	1/4	3		ENSP00000454318

Frequencies

GnomAD3 genomes

AF:

0.0746

AC:

11351

AN:

152178

Hom.:

478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0586

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.00905

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.0633

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.0732

GnomAD3 exomes

AF:

0.0666

AC:

16739

AN:

251310

Hom.:

717

AF XY:

0.0674

AC XY:

9159

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.0804

Gnomad EAS exome

AF:

0.00761

Gnomad SAS exome

AF:

0.0353

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.0712

GnomAD4 exome

AF:

0.0863

AC:

126177

AN:

1461852

Hom.:

5895

Cov.:

AF XY:

0.0848

AC XY:

61642

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0717

Gnomad4 AMR exome

AF:

0.0411

Gnomad4 ASJ exome

AF:

0.0781

Gnomad4 EAS exome

AF:

0.00877

Gnomad4 SAS exome

AF:

0.0374

Gnomad4 FIN exome

AF:

0.0691

Gnomad4 NFE exome

AF:

0.0966

Gnomad4 OTH exome

AF:

0.0798

GnomAD4 genome

AF:

0.0746

AC:

11358

AN:

152296

Hom.:

478

Cov.:

AF XY:

0.0712

AC XY:

5305

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0711

Gnomad4 AMR

AF:

0.0585

Gnomad4 ASJ

AF:

0.0832

Gnomad4 EAS

AF:

0.00907

Gnomad4 SAS

AF:

0.0356

Gnomad4 FIN

AF:

0.0633

Gnomad4 NFE

AF:

0.0900

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0855

Hom.:

1539

Bravo

AF:

0.0763

TwinsUK

AF:

0.0992

AC:

368

ALSPAC

AF:

0.0996

AC:

384

ESP6500AA

AF:

0.0692

AC:

305

ESP6500EA

AF:

0.0887

AC:

763

ExAC

AF:

0.0678

AC:

8227

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0894

EpiControl

AF:

0.0884

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0020

DANN

Benign

0.27

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.19

T;T;.;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.31

N;.;.;N

REVEL

Benign

0.052

Sift

Benign

0.76

T;.;.;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.028

MPC

0.24

ClinPred

0.0029

GERP RS

-9.9

Varity_R

0.013

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over