Variant chr15-79845230-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006441.4(MTHFS):c.592G>A(p.Glu198Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,614,048 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 Benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

MTHFS
NM_006441.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.19

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0067203045).

BP6

Variant 15-79845230-C-T is Benign according to our data. Variant chr15-79845230-C-T is described in ClinVar as [Benign]. Clinvar id is 2169809.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTHFS	NM_006441.4 linkuse as main transcript	c.592G>A	p.Glu198Lys	missense_variant	3/3	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2 linkuse as main transcript	c.520G>A	p.Glu174Lys	missense_variant	4/4		NP_001186689.1
MTHFS	NM_001199758.1 linkuse as main transcript	c.421G>A	p.Glu141Lys	missense_variant	3/3		NP_001186687.1
MTHFS	NR_037654.2 linkuse as main transcript	n.699G>A		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.592G>A	p.Glu198Lys	missense_variant	3/3	1	NM_006441.4	ENSP00000258874	P1	P49914-1
MTHFS	ENST00000559722.2 linkuse as main transcript	c.679G>A	p.Glu227Lys	missense_variant	3/3	2		ENSP00000489076
MTHFS	ENST00000560261.1 linkuse as main transcript	c.100G>A	p.Glu34Lys	missense_variant, NMD_transcript_variant	1/4	3		ENSP00000454318

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000529

AC:

133

AN:

251380

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000258

AC:

377

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

186

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00991

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000210

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Jul 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;.;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;.;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.8

M;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.97

N;.;.;N

REVEL

Uncertain

0.31

Sift

Benign

0.18

T;.;.;T

Sift4G

Benign

0.63

T;T;T;T

Polyphen

0.93

P;.;.;.

Vest4

0.47

MVP

0.64

MPC

0.31

ClinPred

0.094

GERP RS

5.8

Varity_R

0.25

gMVP

0.70

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