19-54174099-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024298.5(MBOAT7):c.1364G>A(p.Arg455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,607,288 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0086 ( 13 hom., cov: 32)

Exomes 𝑓: 0.011 ( 101 hom. )

Consequence

MBOAT7
NM_024298.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0690

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 57
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MBOAT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027557313).

BP6

Variant 19-54174099-C-T is Benign according to our data. Variant chr19-54174099-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00856 (1303/152152) while in subpopulation NFE AF = 0.0133 (907/67988). AF 95% confidence interval is 0.0126. There are 13 homozygotes in GnomAd4. There are 590 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBOAT7	NM_024298.5 link	c.1364G>A	p.Arg455Gln	missense_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.1364G>A	p.Arg455Gln	missense_variant	Exon 8 of 8	1	NM_024298.5	ENSP00000245615.1		Q96N66-1

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1299

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00857

AC:

2077

AN:

242364

AF XY:

0.00892

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.000113

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0109

AC:

15862

AN:

1455136

Hom.:

101

Cov.:

AF XY:

0.0107

AC XY:

7728

AN XY:

723862

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

32980

American (AMR)

AF:

0.00233

AC:

102

AN:

43778

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

477

AN:

25782

East Asian (EAS)

AF:

0.0000761

AC:

AN:

39414

South Asian (SAS)

AF:

0.00337

AC:

289

AN:

85768

European-Finnish (FIN)

AF:

0.0123

AC:

653

AN:

53140

Middle Eastern (MID)

AF:

0.00353

AC:

AN:

4810

European-Non Finnish (NFE)

AF:

0.0123

AC:

13671

AN:

1109478

Other (OTH)

AF:

0.0101

AC:

606

AN:

59986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

836

1671

2507

3342

4178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.00856

AC:

1303

AN:

152152

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

590

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

41446

American (AMR)

AF:

0.00490

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00352

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0101

AC:

107

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

907

AN:

67988

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00628

Hom.:

Bravo

AF:

0.00703

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0138

AC:

119

ExAC

AF:

0.00960

AC:

1165

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 10, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MBOAT7: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.16

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L

PhyloP100

0.069

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.029

Sift

Benign

0.061

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.028

B;B;B

Vest4

0.10

MVP

0.28

MPC

0.20

ClinPred

0.010

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.31

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over