8-30132423-A-T

Position:

• chr8-30132423-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001100916.2(MBOAT4):​c.828T>A​(p.Gly276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBOAT4 NM_001100916.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084083885).
• BP6: Variant 8-30132423-A-T is Benign according to our data. Variant chr8-30132423-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 742348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT4	NM_001100916.2	c.828T>A	p.Gly276=	synonymous_variant	3/3	ENST00000320542.4
LEPROTL1	NM_001128208.2	c.280-4849A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4	c.828T>A	p.Gly276=	synonymous_variant	3/3	1	NM_001100916.2	P1
LEPROTL1	ENST00000442880.6	c.328A>T	p.Thr110Ser	missense_variant	4/5	2
LEPROTL1	ENST00000523116.5	c.280-4849A>T		intron_variant		2
LEPROTL1	ENST00000520739.5	c.279+27937A>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.81
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.010
Sift	Benign	0.29	T
Sift4G	Benign	0.63	T
Vest4		0.061
MutPred		0.34		Gain of disorder (P = 0.034);
MVP		0.043
ClinPred		0.051	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1585481416; hg19: chr8-29989939;