NM_012079.6:c.743C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012079.6(DGAT1):c.743C>A(p.Thr248Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,534,330 control chromosomes in the GnomAD database, including 6,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 383 hom., cov: 33)

Exomes 𝑓: 0.089 ( 5942 hom. )

Consequence

DGAT1
NM_012079.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.26

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

congenital diarrhea 7 with exudative enteropathy
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

DGAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024031997).

BP6

Variant 8-144318103-G-T is Benign according to our data. Variant chr8-144318103-G-T is described in ClinVar as Benign. ClinVar VariationId is 402587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012079.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT1	NM_012079.6	MANE Select	c.743C>A	p.Thr248Asn	missense	Exon 8 of 17	NP_036211.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DGAT1	ENST00000528718.6	TSL:1 MANE Select	c.743C>A	p.Thr248Asn	missense	Exon 8 of 17	ENSP00000482264.1
DGAT1	ENST00000524844.1	TSL:3	n.128C>A		non_coding_transcript_exon	Exon 2 of 7
DGAT1	ENST00000524965.5	TSL:5	n.301C>A		non_coding_transcript_exon	Exon 4 of 12

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9400

AN:

152220

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0653

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.0456

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0949

Gnomad OTH

AF:

0.0845

GnomAD2 exomes

AF:

0.0645

AC:

12270

AN:

190260

AF XY:

0.0670

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.000180

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0968

Gnomad OTH exome

AF:

0.0772

GnomAD4 exome

AF:

0.0889

AC:

122883

AN:

1381992

Hom.:

5942

Cov.:

AF XY:

0.0879

AC XY:

59631

AN XY:

678752

show subpopulations

African (AFR)

AF:

0.0132

AC:

409

AN:

31022

American (AMR)

AF:

0.0500

AC:

1652

AN:

33046

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

1274

AN:

20664

East Asian (EAS)

AF:

0.000154

AC:

AN:

39036

South Asian (SAS)

AF:

0.0430

AC:

3153

AN:

73340

European-Finnish (FIN)

AF:

0.0473

AC:

2349

AN:

49610

Middle Eastern (MID)

AF:

0.0686

AC:

370

AN:

5394

European-Non Finnish (NFE)

AF:

0.102

AC:

109081

AN:

1073020

Other (OTH)

AF:

0.0807

AC:

4589

AN:

56860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

6145

12290

18434

24579

30724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4010

8020

12030

16040

20050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0617

AC:

9397

AN:

152338

Hom.:

383

Cov.:

AF XY:

0.0589

AC XY:

4390

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0183

AC:

760

AN:

41574

American (AMR)

AF:

0.0652

AC:

998

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0379

AC:

183

AN:

4828

European-Finnish (FIN)

AF:

0.0456

AC:

484

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0949

AC:

6454

AN:

68026

Other (OTH)

AF:

0.0865

AC:

183

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0776

Hom.:

801

Bravo

AF:

0.0625

TwinsUK

AF:

0.0933

AC:

346

ALSPAC

AF:

0.108

AC:

416

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.100

AC:

859

ExAC

AF:

0.0641

AC:

7731

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 24, 2020

GeneDx

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: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: Frequency

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

1.3

PrimateAI

Uncertain

0.63

Sift4G

Benign

0.14

Polyphen

0.089

Vest4

0.11

ClinPred

0.0053

GERP RS

3.8

Varity_R

0.20

gMVP

0.74

Mutation Taster

=63/37

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over