rs11841583

chr13-30921042-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_032849.4(MEDAG):c.417G>A(p.Thr139=) 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. In-silico tool predicts a benign outcome for this variant. 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

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEDAG	NM_032849.4	c.417G>A	p.Thr139=	synonymous_variant	3/5	ENST00000380482.9
TEX26-AS1	NR_038287.1	n.1437+9759C>T		intron_variant, non_coding_transcript_variant
MEDAG	XM_017020801.2	c.-37G>A		5_prime_UTR_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEDAG	ENST00000380482.9	c.417G>A	p.Thr139=	synonymous_variant	3/5	1	NM_032849.4	P1
TEX26-AS1	ENST00000585870.6	n.1437+9759C>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.0902 AC: 22646 AN: 251104 Hom.: 1232 AF XY: 0.0860 AC XY: 11667 AN XY: 135698

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 SAS exome AF: 0.0598

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0350

Gnomad4 EAS exome AF: 0.0153

Gnomad4 SAS exome AF: 0.0597

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0889

Gnomad4 OTH exome AF: 0.0843

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0577

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0868 Hom.: 1178

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	6.4
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs11841583; hg19: chr13-31495179; COSMIC: COSV66850327; COSMIC: COSV66850327;