13-30921042-G-A

Variant names:

• chr13-30921042-G-A
• rs11841583
• NM_032849.4:c.417G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_032849.4(MEDAG):​c.417G>A​(p.Thr139Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,613,350 control chromosomes in the GnomAD database, including 7,679 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1301 hom., cov: 33)
  • Exomes 𝑓: 0.088 (6378 hom.)
• Consequence: MEDAG NM_032849.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 11 publications found

Genes affected

MEDAG (HGNC:25926): (mesenteric estrogen dependent adipogenesis) Predicted to be involved in positive regulation of fat cell differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TEX26-AS1 (HGNC:42784): (TEX26 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-0.133 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032849.4. 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
	MEDAG	NM_032849.4	MANE Select	c.417G>A	p.Thr139Thr	synonymous	Exon 3 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1437+9759C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.417G>A	p.Thr139Thr	synonymous	Exon 3 of 5	ENSP00000369849.4	Q5VYS4-1
	MEDAG	ENST00000904728.1		c.417G>A	p.Thr139Thr	synonymous	Exon 3 of 5	ENSP00000574787.1
	MEDAG	ENST00000428944.1	TSL:5	c.225G>A	p.Thr75Thr	synonymous	Exon 3 of 4	ENSP00000416838.1	H0Y831

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17912 AN: 152052 Hom.: 1289 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0902 AC: 22646 AN: 251104 AF XY: 0.0860

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0342

Gnomad EAS exome AF: 0.0185

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0857

Gnomad OTH exome AF: 0.0819

GnomAD4 exome AF: 0.0885 AC: 129313 AN: 1461180 Hom.: 6378 Cov.: 31 AF XY: 0.0865 AC XY: 62870 AN XY: 726902

African (AFR) AF: 0.200 AC: 6707 AN: 33462

American (AMR) AF: 0.116 AC: 5174 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0350 AC: 914 AN: 26132

East Asian (EAS) AF: 0.0153 AC: 608 AN: 39700

South Asian (SAS) AF: 0.0597 AC: 5149 AN: 86194

European-Finnish (FIN) AF: 0.123 AC: 6543 AN: 53408

Middle Eastern (MID) AF: 0.0584 AC: 337 AN: 5766

European-Non Finnish (NFE) AF: 0.0889 AC: 98793 AN: 1111446

Other (OTH) AF: 0.0843 AC: 5088 AN: 60376

GnomAD4 genome AF: 0.118 AC: 17962 AN: 152170 Hom.: 1301 Cov.: 33 AF XY: 0.118 AC XY: 8767 AN XY: 74404

African (AFR) AF: 0.200 AC: 8293 AN: 41492

American (AMR) AF: 0.112 AC: 1706 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3468

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5188

South Asian (SAS) AF: 0.0577 AC: 278 AN: 4822

European-Finnish (FIN) AF: 0.128 AC: 1353 AN: 10574

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5838 AN: 68024

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0900 Hom.: 1665

Bravo AF: 0.120

Asia WGS AF: 0.0590 AC: 207 AN: 3478

EpiCase AF: 0.0790

EpiControl AF: 0.0809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.4
DANN	Benign	0.66
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11841583; hg19: chr13-31495179; COSMIC: COSV66850327; COSMIC: COSV66850327;