8-30132627-C-A

Variant names:

• chr8-30132627-C-A
• rs145757853
• NM_001100916.2:c.624G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100916.2(MBOAT4):​c.624G>T​(p.Arg208Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,551,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: MBOAT4 NM_001100916.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.360

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07481721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBOAT4	NM_001100916.2	c.624G>T	p.Arg208Ser	missense_variant	Exon 3 of 3	ENST00000320542.4	NP_001094386.1
LEPROTL1	NM_001128208.2	c.280-4645C>A		intron_variant	Intron 3 of 3		NP_001121680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBOAT4	ENST00000320542.4	c.624G>T	p.Arg208Ser	missense_variant	Exon 3 of 3	1	NM_001100916.2	ENSP00000314196.3
LEPROTL1	ENST00000523116.5	c.280-4645C>A		intron_variant	Intron 3 of 3	2		ENSP00000428281.1
LEPROTL1	ENST00000442880.6	c.394+138C>A		intron_variant	Intron 4 of 4	2		ENSP00000412803.2
LEPROTL1	ENST00000520739.5	n.279+28141C>A		intron_variant	Intron 3 of 5	4		ENSP00000429398.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.0000576 AC: 9 AN: 156262 Hom.: 0 AF XY: 0.0000845 AC XY: 7 AN XY: 82806

Gnomad AFR exome AF: 0.000630

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000439

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000222 AC: 31 AN: 1399446 Hom.: 0 Cov.: 34 AF XY: 0.0000203 AC XY: 14 AN XY: 690234

Gnomad4 AFR exome AF: 0.000633

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000103

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74374

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000957

Alfa AF: 0.0000953 Hom.: 0

Bravo AF: 0.000227

ExAC AF: 0.0000383 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.624G>T (p.R208S) alteration is located in exon 3 (coding exon 3) of the MBOAT4 gene. This alteration results from a G to T substitution at nucleotide position 624, causing the arginine (R) at amino acid position 208 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		0.27	B
Vest4		0.34
MutPred		0.72		Loss of MoRF binding (P = 0.0491);
MVP		0.44
ClinPred		0.030	T
GERP RS		0.87
Varity_R		0.41
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs145757853; hg19: chr8-29990143;