NM_024298.5:c.1364G>T

Variant names:

• chr19-54174099-C-A
• rs79199039
• NM_024298.5:c.1364G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024298.5(MBOAT7):​c.1364G>T​(p.Arg455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MBOAT7 NM_024298.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 0 publications found

Genes affected

MBOAT7 (HGNC:15505): (membrane bound O-acyltransferase domain containing 7) This gene encodes a member of the membrane-bound O-acyltransferases family of integral membrane proteins that have acyltransferase activity. The encoded protein is a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. This protein is involved in the reacylation of phospholipids as part of the phospholipid remodeling pathway known as the Land cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

MBOAT7 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal recessive 57

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09963328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024298.5. 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
	MBOAT7	NM_024298.5	MANE Select	c.1364G>T	p.Arg455Leu	missense	Exon 8 of 8	NP_077274.3
	MBOAT7	NM_001146056.3		c.1145G>T	p.Arg382Leu	missense	Exon 6 of 6	NP_001139528.1	Q96N66-2
	MBOAT7	NM_001146083.3		c.1145G>T	p.Arg382Leu	missense	Exon 7 of 7	NP_001139555.1	Q96N66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBOAT7	ENST00000245615.6	TSL:1 MANE Select	c.1364G>T	p.Arg455Leu	missense	Exon 8 of 8	ENSP00000245615.1	Q96N66-1
	MBOAT7	ENST00000431666.6	TSL:1	c.1145G>T	p.Arg382Leu	missense	Exon 7 of 7	ENSP00000410503.2	Q96N66-2
	MBOAT7	ENST00000437868.5	TSL:1	n.*1024G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000404915.1	F8WD95

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455184 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 723896

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32980

American (AMR) AF: 0.0000228 AC: 1 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25784

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4810

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109506

Other (OTH) AF: 0.00 AC: 0 AN: 59986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0404278), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.33	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.069
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.055
Sift	Uncertain	0.017	D
Sift4G	Benign	0.17	T
Polyphen		0.49	P
Vest4		0.30
MutPred		0.34		Loss of solvent accessibility (P = 0.0098)
MVP		0.26
MPC		0.22
ClinPred		0.89	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.44
Mutation Taster		=84/16	polymorphism

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: rs79199039; hg19: chr19-54677793;