rs7575835

Positions:

• chr2-110222769-A-G
• chr2-110222769-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414416.2(MTLN):​c.-797T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,772 control chromosomes in the GnomAD database, including 16,801 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 0.45 (16801 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MTLN ENST00000414416.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

MTLN (HGNC:27339): (mitoregulin) Involved in several processes, including fatty acid beta-oxidation; positive regulation of mitochondrial membrane potential; and triglyceride homeostasis. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.110222769A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTLN	ENST00000414416.2	c.-797T>C		5_prime_UTR_variant	2/9	1		ENSP00000485216.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68683 AN: 151648 Hom.: 16752 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.453 AC: 68800 AN: 151766 Hom.: 16801 Cov.: 31 AF XY: 0.454 AC XY: 33697 AN XY: 74160

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.438

Alfa AF: 0.386 Hom.: 19588

Bravo AF: 0.470

Asia WGS AF: 0.547 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.71

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: rs7575835; hg19: chr2-110980346;