NM_001100916.2:c.1157C>T

Variant names:

• chr8-30132094-G-A
• rs1803028273
• NM_001100916.2:c.1157C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001100916.2(MBOAT4):​c.1157C>T​(p.Thr386Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: MBOAT4 NM_001100916.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.21
• Publications: 0 publications found

Genes affected

MBOAT4 (HGNC:32311): (membrane bound O-acyltransferase domain containing 4) Enables serine O-acyltransferase activity. Involved in peptidyl-serine octanoylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LEPROTL1 (HGNC:6555): (leptin receptor overlapping transcript like 1) Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100916.2. 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
	MBOAT4	NM_001100916.2	MANE Select	c.1157C>T	p.Thr386Ile	missense	Exon 3 of 3	NP_001094386.1	Q96T53-1
	LEPROTL1	NM_001128208.2		c.280-5178G>A		intron	N/A	NP_001121680.1	O95214-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBOAT4	ENST00000320542.4	TSL:1 MANE Select	c.1157C>T	p.Thr386Ile	missense	Exon 3 of 3	ENSP00000314196.3	Q96T53-1
	LEPROTL1	ENST00000520682.5	TSL:5	c.398G>A	p.Gly133Asp	missense	Exon 4 of 4	ENSP00000429656.1	E5RHU8
	LEPROTL1	ENST00000523116.5	TSL:2	c.280-5178G>A		intron	N/A	ENSP00000428281.1	O95214-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399466 Hom.: 0 Cov.: 34 AF XY: 0.00000435 AC XY: 3 AN XY: 690230

African (AFR) AF: 0.00 AC: 0 AN: 31600

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078984

Other (OTH) AF: 0.0000172 AC: 1 AN: 58028

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions as Germline

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	0.81
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0046	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.77	T
PhyloP100		8.2
PROVEAN	Benign	0.34	N
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
MutPred		0.061		Loss of catalytic residue at V134 (P = 0.1061)
MVP		0.32
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.72
Mutation Taster		=34/66	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: rs1803028273; hg19: chr8-29989610;