19-54174113-G-T

Variant names:

• chr19-54174113-G-T
• NM_024298.5:c.1350C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024298.5(MBOAT7):​c.1350C>A​(p.Gly450Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MBOAT7 NM_024298.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-54174113-G-T is Benign according to our data. Variant chr19-54174113-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.

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.1350C>A	p.Gly450Gly	synonymous	Exon 8 of 8	NP_077274.3
	MBOAT7	NM_001146056.3		c.1131C>A	p.Gly377Gly	synonymous	Exon 6 of 6	NP_001139528.1	Q96N66-2
	MBOAT7	NM_001146083.3		c.1131C>A	p.Gly377Gly	synonymous	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.1350C>A	p.Gly450Gly	synonymous	Exon 8 of 8	ENSP00000245615.1	Q96N66-1
	MBOAT7	ENST00000431666.6	TSL:1	c.1131C>A	p.Gly377Gly	synonymous	Exon 7 of 7	ENSP00000410503.2	Q96N66-2
	MBOAT7	ENST00000437868.5	TSL:1	n.*1010C>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000404915.1	F8WD95

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453488 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723048

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 43320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25628

East Asian (EAS) AF: 0.00 AC: 0 AN: 39314

South Asian (SAS) AF: 0.00 AC: 0 AN: 85540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5122

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108616

Other (OTH) AF: 0.00 AC: 0 AN: 59896

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.3
DANN	Benign	0.91
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr19-54677807;