chr2-222689414-C-T

Variant names:

• chr2-222689414-C-T
• rs77567312
• NM_058165.3:c.423C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_058165.3(MOGAT1):​c.423C>T​(p.His141His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,613,980 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (21 hom.)
• Consequence: MOGAT1 NM_058165.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.518
• Publications: 1 publications found

Genes affected

MOGAT1 (HGNC:18210): (monoacylglycerol O-acyltransferase 1) Acyl-CoA:monoacylglycerol acyltransferase (MOGAT; EC 2.3.1.22) catalyzes the synthesis of diacylglycerols, the precursor of physiologically important lipids such as triacylglycerol and phospholipids (Yen et al., 2002 [PubMed 12077311]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-222689414-C-T is Benign according to our data. Variant chr2-222689414-C-T is described in ClinVar as Benign. ClinVar VariationId is 714169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.518 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00733 (1116/152284) while in subpopulation AFR AF = 0.0249 (1034/41544). AF 95% confidence interval is 0.0236. There are 13 homozygotes in GnomAd4. There are 540 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058165.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGAT1	NM_058165.3	MANE Select	c.423C>T	p.His141His	synonymous	Exon 3 of 6	NP_477513.2	Q96PD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGAT1	ENST00000446656.4	TSL:5 MANE Select	c.423C>T	p.His141His	synonymous	Exon 3 of 6	ENSP00000406674.3	Q96PD6

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 1110 AN: 152166 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00234 AC: 582 AN: 249002 AF XY: 0.00189

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000945 AC: 1382 AN: 1461696 Hom.: 21 Cov.: 31 AF XY: 0.000941 AC XY: 684 AN XY: 727130

African (AFR) AF: 0.0258 AC: 864 AN: 33478

American (AMR) AF: 0.00119 AC: 53 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00391 AC: 337 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111860

Other (OTH) AF: 0.00167 AC: 101 AN: 60374

GnomAD4 genome AF: 0.00733 AC: 1116 AN: 152284 Hom.: 13 Cov.: 33 AF XY: 0.00725 AC XY: 540 AN XY: 74458

African (AFR) AF: 0.0249 AC: 1034 AN: 41544

American (AMR) AF: 0.00314 AC: 48 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00288 Hom.: 2

Bravo AF: 0.00825

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.19
DANN	Benign	0.47
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs77567312; hg19: chr2-223554133;