1-39955401-C-T

Variant names:

• chr1-39955401-C-T
• rs189000715
• NM_032793.5:c.93+16C>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.93+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: MFSD2A NM_032793.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 0 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=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032793.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2A	NM_032793.5	MANE Select	c.93+16C>T		intron	N/A	NP_116182.2
	MFSD2A	NM_001136493.3		c.93+16C>T		intron	N/A	NP_001129965.1	Q8NA29-1
	MFSD2A	NM_001349821.2		c.87+22C>T		intron	N/A	NP_001336750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2A	ENST00000372811.10	TSL:1 MANE Select	c.93+16C>T		intron	N/A	ENSP00000361898.6	Q8NA29-2
	MFSD2A	ENST00000483824.5	TSL:1	n.228+16C>T		intron	N/A
	MFSD2A	ENST00000372809.5	TSL:2	c.93+16C>T		intron	N/A	ENSP00000361895.5	Q8NA29-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358594 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 667012

African (AFR) AF: 0.00 AC: 0 AN: 30014

American (AMR) AF: 0.00 AC: 0 AN: 30072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20460

East Asian (EAS) AF: 0.00 AC: 0 AN: 35906

South Asian (SAS) AF: 0.00 AC: 0 AN: 71344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5352

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061438

Other (OTH) AF: 0.00 AC: 0 AN: 55908

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.070
PromoterAI		-0.031	Neutral

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: rs189000715; hg19: chr1-40421073;