rs55907012

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012079.6(DGAT1):c.455A>G(p.Lys152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,608,698 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 26 hom., cov: 33)

Exomes 𝑓: 0.017 ( 260 hom. )

Consequence

DGAT1
NM_012079.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

DGAT1 (HGNC:2843): (diacylglycerol O-acyltransferase 1) This gene encodes an multipass transmembrane protein that functions as a key metabolic enzyme. The encoded protein catalyzes the conversion of diacylglycerol and fatty acyl CoA to triacylglycerol. This enzyme can also transfer acyl CoA to retinol. Activity of this protein may be associated with obesity and other metabolic diseases. [provided by RefSeq, Jul 2013]

DGAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041535497).

BP6

Variant 8-144318712-T-C is Benign according to our data. Variant chr8-144318712-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 402589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144318712-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1964/152308) while in subpopulation NFE AF= 0.0195 (1327/68016). AF 95% confidence interval is 0.0186. There are 26 homozygotes in gnomad4. There are 861 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT1	NM_012079.6 link	c.455A>G	p.Lys152Arg	missense_variant	Exon 5 of 17	ENST00000528718.6	NP_036211.2	O75907

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6 link	c.455A>G	p.Lys152Arg	missense_variant	Exon 5 of 17	1	NM_012079.6	ENSP00000482264.1		O75907

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1965

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0137

AC:

3257

AN:

238336

Hom.:

AF XY:

0.0141

AC XY:

1822

AN XY:

129294

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00613

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0172

AC:

25019

AN:

1456390

Hom.:

260

Cov.:

AF XY:

0.0169

AC XY:

12249

AN XY:

723992

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00585

Gnomad4 FIN exome

AF:

0.00407

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0129

AC:

1964

AN:

152308

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

861

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.0195

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0133

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0219

AC:

188

ExAC

AF:

0.0133

AC:

1609

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1.6% of total chromosomes in ExAC, 2.4% European chromosomes -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.31

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.86

.;N

REVEL

Benign

0.043

Sift

Benign

0.28

.;T

Sift4G

Benign

0.82

T;T

Polyphen

0.011

B;.

Vest4

0.20

MPC

0.22

ClinPred

0.0051

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.13

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over