1-39968099-A-T

Variant names:

• chr1-39968099-A-T
• rs3103778
• NM_032793.5:c.1208+183A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032793.5(MFSD2A):​c.1208+183A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFSD2A NM_032793.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 15, primary, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD2A	NM_032793.5	c.1208+183A>T		intron_variant	Intron 11 of 13	ENST00000372811.10	NP_116182.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD2A	ENST00000372811.10	c.1208+183A>T		intron_variant	Intron 11 of 13	1	NM_032793.5	ENSP00000361898.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 489578 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 256728

African (AFR) AF: 0.00 AC: 0 AN: 13102

American (AMR) AF: 0.00 AC: 0 AN: 18856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14012

East Asian (EAS) AF: 0.00 AC: 0 AN: 31484

South Asian (SAS) AF: 0.00 AC: 0 AN: 45414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2054

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 306244

Other (OTH) AF: 0.00 AC: 0 AN: 27456

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.50
PhyloP100		-0.074

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

Other links and lift over

dbSNP: rs3103778; hg19: chr1-40433771;