dbSNP rs778077707: MTHFSD:p.Gly315Glu (chr16-86532219-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001159377.2(MTHFSD):c.944G>A(p.Gly315Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,582,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MTHFSD
NM_001159377.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.164

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03736314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTHFSD	NM_001159377.2	MANE Select	c.944G>A	p.Gly315Glu	missense	Exon 8 of 8	NP_001152849.1	Q2M296-1
MTHFSD	NM_001159378.2		c.944G>A	p.Gly315Glu	missense	Exon 8 of 8	NP_001152850.1	Q2M296-3
MTHFSD	NM_001159379.2		c.941G>A	p.Gly314Glu	missense	Exon 8 of 8	NP_001152851.1	Q2M296-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTHFSD	ENST00000360900.11	TSL:1 MANE Select	c.944G>A	p.Gly315Glu	missense	Exon 8 of 8	ENSP00000354152.6	Q2M296-1
MTHFSD	ENST00000381214.9	TSL:1	c.944G>A	p.Gly315Glu	missense	Exon 8 of 8	ENSP00000370612.5	Q2M296-3
MTHFSD	ENST00000543303.6	TSL:1	c.941G>A	p.Gly314Glu	missense	Exon 8 of 8	ENSP00000444003.2	Q2M296-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000527

AC:

AN:

208776

AF XY:

0.0000262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000746

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000259

AC:

AN:

1430534

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

709154

show subpopulations

African (AFR)

AF:

0.0000615

AC:

AN:

32500

American (AMR)

AF:

0.00

AC:

AN:

40502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24500

East Asian (EAS)

AF:

0.00

AC:

AN:

38396

South Asian (SAS)

AF:

0.0000857

AC:

AN:

81670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0000228

AC:

AN:

1097032

Other (OTH)

AF:

0.0000510

AC:

AN:

58878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000665

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.017

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.098

M_CAP

Benign

0.0033

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.51

PhyloP100

-0.16

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.11

REVEL

Benign

0.013

Sift

Benign

0.29

Sift4G

Benign

0.33

Polyphen

0.033

Vest4

0.14

MutPred

0.33

Loss of sheet (P = 0.0457)

MVP

0.095

MPC

0.024

ClinPred

0.065

GERP RS

-8.5

Varity_R

0.068

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over