Variant 4-74199824-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001144978.3(MTHFD2L):c.482G>A(p.Gly161Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,612,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

MTHFD2L
NM_001144978.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

MTHFD2L (HGNC:31865): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like) Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Predicted to be located in mitochondrial matrix. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MTHFD2L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012388945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD2L	NM_001144978.3 linkuse as main transcript	c.482G>A	p.Gly161Glu	missense_variant	4/8	ENST00000325278.7	NP_001138450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD2L	ENST00000325278.7 linkuse as main transcript	c.482G>A	p.Gly161Glu	missense_variant	4/8	5	NM_001144978.3	ENSP00000321984	P1	Q9H903-4

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000656

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00135

AC:

338

AN:

250462

Hom.:

AF XY:

0.00140

AC XY:

189

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000879

Gnomad NFE exome

AF:

0.00241

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00162

AC:

2367

AN:

1460146

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1160

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152106

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000850

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00107

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00161

AC:

196

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpretted as Uncertain significance and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.7

.;N;.;.

MutationTaster

Benign

0.87

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.030

D;D;D;D

Sift4G

Uncertain

0.043

D;D;D;D

Polyphen

0.74

.;P;.;.

Vest4

0.36

MVP

0.44

MPC

0.45

ClinPred

0.94

GERP RS

4.3

Varity_R

0.31

gMVP

0.87

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