8-144316596-G-C

Variant names:

• chr8-144316596-G-C
• rs1031073510
• NM_012079.6:c.1425C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012079.6(DGAT1):​c.1425C>G​(p.Asp475Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DGAT1 NM_012079.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT1	NM_012079.6	c.1425C>G	p.Asp475Glu	missense_variant	Exon 17 of 17	ENST00000528718.6	NP_036211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6	c.1425C>G	p.Asp475Glu	missense_variant	Exon 17 of 17	1	NM_012079.6	ENSP00000482264.1
DGAT1	ENST00000332324.5	c.928C>G	p.Leu310Val	missense_variant	Exon 10 of 10	5		ENSP00000332258.5
DGAT1	ENST00000524965.5	n.1060C>G		non_coding_transcript_exon_variant	Exon 12 of 12	5
DGAT1	ENST00000527885.1	n.*247C>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453268 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.7	H
PrimateAI	Uncertain	0.65	T
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.74
MutPred		0.62		Loss of sheet (P = 0.0817);
MVP		0.60
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.75

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: rs1031073510; hg19: chr8-145540259;