8-30132484-T-G

Variant names:

• chr8-30132484-T-G
• rs1444206382
• NM_001100916.2:c.767A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100916.2(MBOAT4):​c.767A>C​(p.Tyr256Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,399,422 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: MBOAT4 NM_001100916.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26188403).

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.767A>C	p.Tyr256Ser	missense	Exon 3 of 3	NP_001094386.1	Q96T53-1
	LEPROTL1	NM_001128208.2		c.280-4788T>G		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.767A>C	p.Tyr256Ser	missense	Exon 3 of 3	ENSP00000314196.3	Q96T53-1
	LEPROTL1	ENST00000442880.6	TSL:2	c.389T>G	p.Val130Gly	missense	Exon 4 of 5	ENSP00000412803.2	C9JVM4
	LEPROTL1	ENST00000523116.5	TSL:2	c.280-4788T>G		intron	N/A	ENSP00000428281.1	O95214-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 155692 AF XY: 0.00

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: 0.0000335

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000286 AC: 40 AN: 1399422 Hom.: 0 Cov.: 34 AF XY: 0.0000217 AC XY: 15 AN XY: 690220

African (AFR) AF: 0.00 AC: 0 AN: 31598

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: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49278

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

European-Non Finnish (NFE) AF: 0.0000334 AC: 36 AN: 1078978

Other (OTH) AF: 0.0000690 AC: 4 AN: 58010

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.71
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.22	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.051	D
PhyloP100		6.6
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Vest4		0.45
MutPred		0.29		Gain of disorder (P = 0.0148)
MVP		0.32
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.96
Mutation Taster		=33/67	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: rs1444206382; hg19: chr8-29990000;