chr8-144316620-T-C

Variant names:

• chr8-144316620-T-C
• NM_012079.6:c.1401A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012079.6(DGAT1):​c.1401A>G​(p.Ile467Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I467I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DGAT1 NM_012079.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08782458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT1	NM_012079.6	c.1401A>G	p.Ile467Met	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.1401A>G	p.Ile467Met	missense_variant	Exon 17 of 17	1	NM_012079.6	ENSP00000482264.1
DGAT1	ENST00000332324.5	c.904A>G	p.Ser302Gly	missense_variant	Exon 10 of 10	5		ENSP00000332258.5
DGAT1	ENST00000524965.5	n.1036A>G		non_coding_transcript_exon_variant	Exon 12 of 12	5
DGAT1	ENST00000527885.1	n.*223A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456234 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724074

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Benign	0.091
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.53
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.43	N
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.22	T
Polyphen		0.056	B
Vest4		0.16
MutPred		0.48		Loss of sheet (P = 0.0817);
MVP		0.39
ClinPred		0.13	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145540283;