Variant chr15-79889117-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006441.4(MTHFS):c.355G>C(p.Val119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,614,186 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

MTHFS
NM_006441.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.727

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006963402).

BP6

Variant 15-79889117-C-G is Benign according to our data. Variant chr15-79889117-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2069160.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTHFS	NM_006441.4 linkuse as main transcript	c.355G>C	p.Val119Leu	missense_variant	2/3	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2 linkuse as main transcript	c.283G>C	p.Val95Leu	missense_variant	3/4		NP_001186689.1
MTHFS	NM_001199758.1 linkuse as main transcript	c.184G>C	p.Val62Leu	missense_variant	2/3		NP_001186687.1
MTHFS	NR_037654.2 linkuse as main transcript	n.462G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000258874.4 linkuse as main transcript	c.355G>C	p.Val119Leu	missense_variant	2/3	1	NM_006441.4	ENSP00000258874	P1	P49914-1
MTHFS	ENST00000559722.2 linkuse as main transcript	c.442G>C	p.Val148Leu	missense_variant	2/3	2		ENSP00000489076
MTHFS	ENST00000560919.5 linkuse as main transcript	c.*301G>C		3_prime_UTR_variant, NMD_transcript_variant	2/2	2		ENSP00000454626

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000533

AC:

134

AN:

251364

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

277

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000302

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000309

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000502

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.1

DANN

Benign

0.93

DEOGEN2

Benign

0.26

T;.;.;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.69

T;T;.;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

L;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.94

N;.;.;N;.

REVEL

Benign

0.038

Sift

Benign

0.32

T;.;.;T;.

Sift4G

Benign

0.31

T;T;T;T;.

Polyphen

0.0

B;.;.;.;.

Vest4

0.097

MVP

0.19

MPC

0.24

ClinPred

0.0081

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.39

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