chr13-30906579-C-T

Variant names:

• chr13-30906579-C-T
• rs776912049
• NM_032849.4:c.64C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032849.4(MEDAG):​c.64C>T​(p.Leu22Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,372 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L22V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MEDAG NM_032849.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27655226).

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.64C>T	p.Leu22Phe	missense	Exon 1 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1438-22519G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.64C>T	p.Leu22Phe	missense	Exon 1 of 5	ENSP00000369849.4	Q5VYS4-1
	MEDAG	ENST00000904728.1		c.64C>T	p.Leu22Phe	missense	Exon 1 of 5	ENSP00000574787.1
	MEDAG	ENST00000968515.1		c.64C>T	p.Leu22Phe	missense	Exon 1 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 206186 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1432372 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 712648

⚠️ 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: 31198

American (AMR) AF: 0.00 AC: 0 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38006

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106494

Other (OTH) AF: 0.00 AC: 0 AN: 59548

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.55		Loss of disorder (P = 0.0918)
MVP		0.52
MPC		0.59
ClinPred		0.91	D
GERP RS		4.0
PromoterAI		0.089	Neutral
Varity_R		0.48
gMVP		0.58
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs776912049; hg19: chr13-31480716;