11-75720004-C-T

Position:

• chr11-75720004-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025098.4(MOGAT2):​c.104C>T​(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,613,896 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (86 hom.)
• Consequence: MOGAT2 NM_025098.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.58

Genes affected

MOGAT2 (HGNC:23248): (monoacylglycerol O-acyltransferase 2) The protein encoded by this gene is an enzyme that catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. The encoded protein is important in the uptake of dietary fat by the small intestine. This protein forms a complex with diacylglycerol O-acyltransferase 2 in the endoplasmic reticulum, and this complex catalyzes the synthesis of triacylglycerol. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013633072).
• BP6: Variant 11-75720004-C-T is Benign according to our data. Variant chr11-75720004-C-T is described in ClinVar as [Benign]. Clinvar id is 781225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOGAT2	NM_025098.4	c.104C>T	p.Thr35Ile	missense_variant	2/6	ENST00000198801.10	NP_079374.2
MOGAT2	XM_024448696.2	c.-143C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6		XP_024304464.1
MOGAT2	XM_011545267.2	c.104C>T	p.Thr35Ile	missense_variant	2/6		XP_011543569.1
MOGAT2	XM_024448696.2	c.-143C>T		5_prime_UTR_variant	2/6		XP_024304464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOGAT2	ENST00000198801.10	c.104C>T	p.Thr35Ile	missense_variant	2/6	1	NM_025098.4	ENSP00000198801.5
MOGAT2	ENST00000526712.1	c.-143C>T		5_prime_UTR_premature_start_codon_gain_variant	1/5	2		ENSP00000436283.1
MOGAT2	ENST00000526712.1	c.-143C>T		5_prime_UTR_variant	1/5	2		ENSP00000436283.1
MOGAT2	ENST00000525093.5	n.104C>T		non_coding_transcript_exon_variant	2/5	2		ENSP00000436537.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2874 AN: 152186 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00539 AC: 1352 AN: 251022 Hom.: 41 AF XY: 0.00383 AC XY: 520 AN XY: 135666

Gnomad AFR exome AF: 0.0705

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00212 AC: 3097 AN: 1461592 Hom.: 86 Cov.: 31 AF XY: 0.00188 AC XY: 1370 AN XY: 727108

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000301

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00503

GnomAD4 genome AF: 0.0190 AC: 2897 AN: 152304 Hom.: 81 Cov.: 32 AF XY: 0.0184 AC XY: 1371 AN XY: 74484

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00825 Hom.: 22

Bravo AF: 0.0219

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0707 AC: 311

ESP6500EA AF: 0.000699 AC: 6

ExAC AF: 0.00663 AC: 805

EpiCase AF: 0.000436

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0010
DANN	Benign	0.77
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.40	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.098
MVP		0.13
MPC		0.11
ClinPred		0.0035	T
GERP RS		-7.3
Varity_R		0.019
gMVP		0.29

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: rs35828061; hg19: chr11-75431049;