Variant 16-86532184-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001159377.2(MTHFSD):c.979C>T(p.Arg327Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,577,504 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MTHFSD
NM_001159377.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0690

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26782262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFSD	NM_001159377.2 linkuse as main transcript	c.979C>T	p.Arg327Trp	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.979C>T	p.Arg327Trp	missense_variant	8/8	1	NM_001159377.2	ENSP00000354152.6		Q2M296-1

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1425830

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

706200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.0000499

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151674

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000664

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000166

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 04, 2021

The c.979C>T (p.R327W) alteration is located in exon 8 (coding exon 8) of the MTHFSD gene. This alteration results from a C to T substitution at nucleotide position 979, causing the arginine (R) at amino acid position 327 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

M;.;.;.;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.9

D;D;.;D;D

REVEL

Benign

0.12

Sift

Benign

0.051

T;D;.;D;D

Sift4G

Uncertain

0.037

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.34

MVP

0.43

MPC

0.16

ClinPred

0.97

GERP RS

0.32

Varity_R

0.67

gMVP

0.54

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