chr1-39958673-AGTT-A

Position:

• chr1-39958673-AGTT-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_032793.5(MFSD2A):​c.229-25_229-23del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MFSD2A NM_032793.5 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.103

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-39958673-AGTT-A is Pathogenic according to our data. Variant chr1-39958673-AGTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 684729.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-39958673-AGTT-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD2A	NM_032793.5	c.229-25_229-23del		intron_variant		ENST00000372811.10	NP_116182.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD2A	ENST00000372811.10	c.229-25_229-23del		intron_variant		1	NM_032793.5	ENSP00000361898	P1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Febrile seizure (within the age range of 3 months to 6 years);C0010417:Cryptorchidism;C0015934:Fetal growth restriction;C1837658:Delayed gross motor development;C3714756:Intellectual disability;C4025898:Functional abnormality of male internal genitalia;C4551563:Microcephaly;C5574662:Hyperammonemia Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Human Genetics Department, Tarbiat Modares University

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1570238098; hg19: chr1-40424345;