13-30906740-C-A

Position:

• chr13-30906740-C-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.225C>A​(p.Asp75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEDAG NM_032849.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.297

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=0.2630164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEDAG	NM_032849.4	c.225C>A	p.Asp75Glu	missense_variant	1/5	ENST00000380482.9
TEX26-AS1	NR_038287.1	n.1438-22680G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEDAG	ENST00000380482.9	c.225C>A	p.Asp75Glu	missense_variant	1/5	1	NM_032849.4	P1
TEX26-AS1	ENST00000585870.6	n.1438-22680G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1358526 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 670704

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000873 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.225C>A (p.D75E) alteration is located in exon 1 (coding exon 1) of the MEDAG gene. This alteration results from a C to A substitution at nucleotide position 225, causing the aspartic acid (D) at amino acid position 75 to be replaced by a glutamic acid (E). 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	Uncertain	0.56
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.70	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.098
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.062	T
Polyphen		0.83	P
Vest4		0.36
MutPred		0.55		Gain of sheet (P = 0.0266);
MVP		0.50
MPC		0.18
ClinPred		0.98	D
GERP RS		2.1
Varity_R		0.29
gMVP		0.63

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: rs749394457; hg19: chr13-31480877;