rs143520373

Variant names:

• chr6-20112994-C-A
• rs143520373
• NM_001080480.3:c.1091G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-20112994-C-A
• chr6-20112994-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001080480.3(MBOAT1):​c.1091G>T​(p.Arg364Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000125 in 1,613,850 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R364Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MBOAT1 NM_001080480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98
• Publications: 4 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92

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.1091G>T	p.Arg364Leu	missense	Exon 11 of 13	NP_001073949.1	Q6ZNC8-1
	MBOAT1	NR_073465.2		n.1046G>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.1091G>T	p.Arg364Leu	missense	Exon 11 of 13	ENSP00000324944.7	Q6ZNC8-1
	MBOAT1	ENST00000969078.1		c.1118G>T	p.Arg373Leu	missense	Exon 12 of 14	ENSP00000639137.1
	MBOAT1	ENST00000883939.1		c.1025G>T	p.Arg342Leu	missense	Exon 11 of 13	ENSP00000553998.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000479 AC: 12 AN: 250724 AF XY: 0.0000443

Gnomad AFR exome AF: 0.0000616

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: 0.0000883

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000133 AC: 194 AN: 1461546 Hom.: 0 Cov.: 31 AF XY: 0.000131 AC XY: 95 AN XY: 727068

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000163 AC: 181 AN: 1111838

Other (OTH) AF: 0.000199 AC: 12 AN: 60378

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152304 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000124 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.92
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		5.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.92
MVP		0.93
MPC		0.36
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.64
gMVP		0.96
Mutation Taster		=26/74	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: rs143520373; hg19: chr6-20113225; COSMIC: COSV100209052;