13-30906640-G-A

Variant names:

• chr13-30906640-G-A
• rs1952832679
• NM_032849.4:c.125G>A

Variant summary

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

The NM_032849.4(MEDAG):​c.125G>A​(p.Arg42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,425,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MEDAG NM_032849.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611

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 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=0.14367995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEDAG	NM_032849.4	c.125G>A	p.Arg42His	missense_variant	Exon 1 of 5	ENST00000380482.9	NP_116238.3
TEX26-AS1	NR_038287.1	n.1438-22580C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEDAG	ENST00000380482.9	c.125G>A	p.Arg42His	missense_variant	Exon 1 of 5	1	NM_032849.4	ENSP00000369849.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1425258 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 708094

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: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.125G>A (p.R42H) alteration is located in exon 1 (coding exon 1) of the MEDAG gene. This alteration results from a G to A substitution at nucleotide position 125, causing the arginine (R) at amino acid position 42 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.060
Sift	Benign	0.080	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.43		Loss of helix (P = 0.0558);
MVP		0.13
MPC		0.38
ClinPred		0.35	T
GERP RS		0.66
Varity_R		0.057
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs1952832679; hg19: chr13-31480777; COSMIC: COSV100995226; COSMIC: COSV100995226;