1-39957115-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032793.5(MFSD2A):​c.122T>G​(p.Leu41Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

MFSD2A
NM_032793.5 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79
Variant links:
Genes affected
MFSD2A (HGNC:25897): (MFSD2 lysolipid transporter A, lysophospholipid) The protein encoded by this gene is a transmembrane protein and sodium-dependent lysophosphatidylcholine transporter. The encoded protein is involved in the establishment of the blood-brain barrier and is required for brain growth and function. Defects in this gene are a cause of a progressive microcephaly syndrome. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MFSD2ANM_032793.5 linkuse as main transcriptc.122T>G p.Leu41Trp missense_variant 2/14 ENST00000372811.10 NP_116182.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MFSD2AENST00000372811.10 linkuse as main transcriptc.122T>G p.Leu41Trp missense_variant 2/141 NM_032793.5 ENSP00000361898 P1Q8NA29-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 26, 2021In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MFSD2A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with tryptophan at codon 41 of the MFSD2A protein (p.Leu41Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
27
DANN
Benign
0.96
DEOGEN2
Benign
0.21
.;T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Uncertain
0.091
D
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Pathogenic
3.3
M;.;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Uncertain
0.62
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.74
MutPred
0.64
Gain of loop (P = 0.0166);.;Gain of loop (P = 0.0166);
MVP
0.043
MPC
1.8
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.66
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40422787; API