Variant 16-86532313-C-T 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_001159377.2(MTHFSD):c.850G>A(p.Gly284Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,589,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MTHFSD
NM_001159377.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

Variant links:

Genes affected

MTHFSD (HGNC:25778): (methenyltetrahydrofolate synthetase domain containing) Enables RNA binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTHFSD links:

MTHFSD (HGNC:):

MTHFSD 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=0.05624181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFSD	NM_001159377.2 linkuse as main transcript	c.850G>A	p.Gly284Arg	missense_variant	8/8	ENST00000360900.11	NP_001152849.1	Q2M296-1B4DN17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFSD	ENST00000360900.11 linkuse as main transcript	c.850G>A	p.Gly284Arg	missense_variant	8/8	1	NM_001159377.2	ENSP00000354152.6		Q2M296-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000487

AC:

AN:

1437754

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

713648

show subpopulations

Gnomad4 AFR exome

AF:

0.0000919

Gnomad4 AMR exome

AF:

0.0000245

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000799

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000260

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.850G>A (p.G284R) alteration is located in exon 8 (coding exon 8) of the MTHFSD gene. This alteration results from a G to A substitution at nucleotide position 850, causing the glycine (G) at amino acid position 284 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.3

DANN

Benign

0.47

DEOGEN2

Benign

0.00067

T;T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.48

T;T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.056

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.;.;L

PrimateAI

Benign

0.39

PROVEAN

Benign

0.63

N;N;.;N;N

REVEL

Benign

0.033

Sift

Benign

0.56

T;T;.;T;T

Sift4G

Benign

0.67

T;T;T;T;T

Polyphen

0.023

B;.;B;.;.

Vest4

0.11

MutPred

0.20

Loss of catalytic residue at P280 (P = 0.1132);.;.;.;Loss of catalytic residue at P280 (P = 0.1132);

MVP

0.13

MPC

0.020

ClinPred

0.0068

GERP RS

-0.67

Varity_R

0.038

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