19-54180772-C-G

Variant names:

• chr19-54180772-C-G
• rs886041060
• ENST00000494142.1:n.19G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The ENST00000494142.1(MBOAT7):​n.19G>C variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBOAT7 ENST00000494142.1 non_coding_transcript_exon
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.65
• Publications: 3 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):

• 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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 19-54180772-C-G is Pathogenic according to our data. Variant chr19-54180772-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 268114.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBOAT7	NM_024298.5	c.854+1G>C		splice_donor_variant, intron_variant	Intron 6 of 7	ENST00000245615.6	NP_077274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBOAT7	ENST00000245615.6	c.854+1G>C		splice_donor_variant, intron_variant	Intron 6 of 7	1	NM_024298.5	ENSP00000245615.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1374826 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 678182

African (AFR) AF: 0.00 AC: 0 AN: 31200

American (AMR) AF: 0.00 AC: 0 AN: 32718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22798

East Asian (EAS) AF: 0.00 AC: 0 AN: 37452

South Asian (SAS) AF: 0.00 AC: 0 AN: 76538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076344

Other (OTH) AF: 0.00 AC: 0 AN: 57050

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal recessive 57 Pathogenic:1

Jan 26, 2022

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	32
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		4.7
GERP RS		4.6
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.89		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.89		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886041060; hg19: chr19-54684489;