dbSNP rs534559168: MFSD2B:p.Arg38Gly (chr2-24013300-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001346880.2(MFSD2B):c.112C>G(p.Arg38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,602,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MFSD2B
NM_001346880.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Publications

0 publications found

Variant links:

Genes affected

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08207661).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346880.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2B	NM_001346880.2	MANE Select	c.112C>G	p.Arg38Gly	missense	Exon 2 of 14	NP_001333809.1	A6NFX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD2B	ENST00000338315.6	TSL:5 MANE Select	c.112C>G	p.Arg38Gly	missense	Exon 2 of 14	ENSP00000342501.4	A6NFX1
MFSD2B	ENST00000495018.1	TSL:1	n.167C>G		non_coding_transcript_exon	Exon 2 of 6
MFSD2B	ENST00000669179.1		c.112C>G	p.Arg38Gly	missense	Exon 2 of 15	ENSP00000499689.1	A0A590UK14

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247270

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.000195

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450736

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719894

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39390

South Asian (SAS)

AF:

0.00

AC:

AN:

85272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104256

Other (OTH)

AF:

0.00

AC:

AN:

59740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

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

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.60

M_CAP

Benign

0.017

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Benign

0.17

Sift4G

Benign

0.13

Polyphen

0.024

Vest4

0.26

MutPred

0.42

Loss of MoRF binding (P = 0.0157)

MVP

0.030

MPC

0.086

ClinPred

0.11

GERP RS

5.5

Varity_R

0.21

gMVP

0.28

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over