dbSNP rs747170388: MFSD2B:p.Leu470Pro (chr2-24024190-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001346880.2(MFSD2B):c.1409T>C(p.Leu470Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MFSD2B
NM_001346880.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD2B	NM_001346880.2 link	c.1409T>C	p.Leu470Pro	missense_variant	Exon 13 of 14	ENST00000338315.6	NP_001333809.1	A6NFX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2B	ENST00000338315.6 link	c.1409T>C	p.Leu470Pro	missense_variant	Exon 13 of 14	5	NM_001346880.2	ENSP00000342501.4		A6NFX1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248578

AF XY:

0.0000148

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461514

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111798

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1409T>C (p.L470P) alteration is located in exon 13 (coding exon 13) of the MFSD2B gene. This alteration results from a T to C substitution at nucleotide position 1409, causing the leucine (L) at amino acid position 470 to be replaced by a proline (P). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

.;D

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.59

T;T

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Uncertain

2.5

.;M

PhyloP100

7.3

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

Vest4

0.83

MutPred

0.64

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.81

MPC

0.46

ClinPred

0.98

GERP RS

4.9

Varity_R

0.88

gMVP

0.86

Mutation Taster

=53/47

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over