13-30917492-C-A

Variant names:

• chr13-30917492-C-A
• rs765309979
• NM_032849.4:c.368C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032849.4(MEDAG):​c.368C>A​(p.Thr123Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T123I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MEDAG NM_032849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20598945).

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.368C>A	p.Thr123Asn	missense	Exon 2 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1437+13309G>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.368C>A	p.Thr123Asn	missense	Exon 2 of 5	ENSP00000369849.4	Q5VYS4-1
	MEDAG	ENST00000904728.1		c.368C>A	p.Thr123Asn	missense	Exon 2 of 5	ENSP00000574787.1
	MEDAG	ENST00000968515.1		c.368C>A	p.Thr123Asn	missense	Exon 2 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439438 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 717618

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32826

American (AMR) AF: 0.00 AC: 0 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 85688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092382

Other (OTH) AF: 0.00 AC: 0 AN: 59602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.066
Sift	Benign	0.051	T
Sift4G	Uncertain	0.060	T
Polyphen		0.98	D
Vest4		0.35
MutPred		0.35		Loss of phosphorylation at T123 (P = 0.0219)
MVP		0.30
MPC		0.14
ClinPred		0.56	D
GERP RS		3.9
Varity_R		0.18
gMVP		0.46
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs765309979; hg19: chr13-31491629; COSMIC: COSV66849833; COSMIC: COSV66849833;