Genetic Variant MFSD2A:c.93+18C>T (chr1-39955403-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_032793.5(MFSD2A):c.93+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,510,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MFSD2A
NM_032793.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.122

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]

MFSD2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-39955403-C-T is Benign according to our data. Variant chr1-39955403-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3628218.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000315 (48/152258) while in subpopulation AMR AF= 0.00268 (41/15298). AF 95% confidence interval is 0.00203. There are 1 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD2A	NM_032793.5 link	c.93+18C>T		intron_variant	Intron 1 of 13	ENST00000372811.10	NP_116182.2	Q8NA29-2Q71RE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2A	ENST00000372811.10 link	c.93+18C>T		intron_variant	Intron 1 of 13	1	NM_032793.5	ENSP00000361898.6		Q8NA29-2

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

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:

0.00239

GnomAD3 exomes

AF:

0.0000299

AC:

AN:

133900

Hom.:

AF XY:

0.00

AC XY:

AN XY:

72428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000643

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1358034

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

666758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000333

Gnomad4 AMR exome

AF:

0.000367

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:

0.00000471

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000315

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000491

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.89

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