Genetic Variant MBOAT7:p.Arg454ProfsTer28 (chr19-54174080-GGGCTGGGATGCTGCCTTCCGCC-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PVS1_ModerateBS1_Supporting

The NM_024298.5(MBOAT7):c.1361_1382delGGCGGAAGGCAGCATCCCAGCC(p.Arg454ProfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,606,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

MBOAT7
NM_024298.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0409 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000381 (58/152154) while in subpopulation AFR AF = 0.0014 (58/41538). AF 95% confidence interval is 0.00111. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBOAT7	NM_024298.5 link	c.1361_1382delGGCGGAAGGCAGCATCCCAGCC	p.Arg454ProfsTer28	frameshift_variant	Exon 8 of 8	ENST00000245615.6	NP_077274.3	Q96N66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBOAT7	ENST00000245615.6 link	c.1361_1382delGGCGGAAGGCAGCATCCCAGCC	p.Arg454ProfsTer28	frameshift_variant	Exon 8 of 8	1	NM_024298.5	ENSP00000245615.1		Q96N66-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000907

AC:

AN:

242672

AF XY:

0.0000531

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1454502

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

723480

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

AC:

AN:

33066

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

43672

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25746

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39402

Gnomad4 SAS exome

AF:

0.0000117

AC:

AN:

85698

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53058

Gnomad4 NFE exome

AF:

9.01e-7

AC:

AN:

1109384

Gnomad4 Remaining exome

AF:

0.0000334

AC:

AN:

59968

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000381

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00140

AC:

0.00139631

AN:

0.00139631

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000502

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal recessive 57

Uncertain:1

Apr 14, 2020

New York Genome Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=38/162

disease causing (long InDel)

Splicing

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