chr6-20112928-C-A

Variant names:

• chr6-20112928-C-A
• rs937217669
• NM_001080480.3:c.1157G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001080480.3(MBOAT1):​c.1157G>T​(p.Gly386Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MBOAT1 NM_001080480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.85
• Publications: 0 publications found

Genes affected

MBOAT1 (HGNC:21579): (membrane bound O-acyltransferase domain containing 1) This gene belongs to the membrane-bound O-acetyltransferase superfamily. The encoded transmembrane protein is an enzyme that transfers organic compounds, preferably from oleoyl-CoA, to hydroxyl groups of protein targets in membranes. A translocation disrupting this gene may be associated with brachydactyly syndactyly syndrome. Alternately spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080480.3. 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
	MBOAT1	NM_001080480.3	MANE Select	c.1157G>T	p.Gly386Val	missense	Exon 11 of 13	NP_001073949.1	Q6ZNC8-1
	MBOAT1	NR_073465.2		n.1112G>T		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBOAT1	ENST00000324607.8	TSL:1 MANE Select	c.1157G>T	p.Gly386Val	missense	Exon 11 of 13	ENSP00000324944.7	Q6ZNC8-1
	MBOAT1	ENST00000969078.1		c.1184G>T	p.Gly395Val	missense	Exon 12 of 14	ENSP00000639137.1
	MBOAT1	ENST00000883939.1		c.1091G>T	p.Gly364Val	missense	Exon 11 of 13	ENSP00000553998.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251256 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.92		Gain of helix (P = 0.2059)
MVP		0.97
MPC		0.36
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.93
gMVP		0.97
Mutation Taster		=18/82	disease causing

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: rs937217669; hg19: chr6-20113159;