19-54174099-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0690
• Publications: 7 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: 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

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>A	p.Arg455Gln	missense	Exon 8 of 8	NP_077274.3
	MBOAT7	NM_001146056.3		c.1145G>A	p.Arg382Gln	missense	Exon 6 of 6	NP_001139528.1	Q96N66-2
	MBOAT7	NM_001146083.3		c.1145G>A	p.Arg382Gln	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>A	p.Arg455Gln	missense	Exon 8 of 8	ENSP00000245615.1	Q96N66-1
	MBOAT7	ENST00000431666.6	TSL:1	c.1145G>A	p.Arg382Gln	missense	Exon 7 of 7	ENSP00000410503.2	Q96N66-2
	MBOAT7	ENST00000437868.5	TSL:1	n.*1024G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000404915.1	F8WD95

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1299 AN: 152032 Hom.: 13 Cov.: 32

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

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.: 31 AF XY: 0.0107 AC XY: 7728 AN XY: 723862

African (AFR) AF: 0.00133 AC: 44 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: 3 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: 17 AN: 4810

European-Non Finnish (NFE) AF: 0.0123 AC: 13671 AN: 1109478

Other (OTH) AF: 0.0101 AC: 606 AN: 59986

GnomAD4 genome AF: 0.00856 AC: 1303 AN: 152152 Hom.: 13 Cov.: 32 AF XY: 0.00793 AC XY: 590 AN XY: 74418

African (AFR) AF: 0.00229 AC: 95 AN: 41446

American (AMR) AF: 0.00490 AC: 75 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4828

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 907 AN: 67988

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00628 Hom.: 14

Bravo AF: 0.00703

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.00960 AC: 1165

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.069
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.029
Sift	Benign	0.061	T
Sift4G	Benign	0.35	T
Polyphen		0.028	B
Vest4		0.10
MVP		0.28
MPC		0.20
ClinPred		0.010	T
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

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; COSMIC: COSV99825176; COSMIC: COSV99825176;