2-110222769-A-G

Variant names:

• chr2-110222769-A-G
• rs7575835
• ENST00000414416.2:c.-797T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTLN	ENST00000414416.2	c.-797T>C		5_prime_UTR_variant	Exon 2 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.623 AC: 25772 AN: 41360

American (AMR) AF: 0.458 AC: 7002 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3099 AN: 5150

South Asian (SAS) AF: 0.517 AC: 2480 AN: 4800

European-Finnish (FIN) AF: 0.281 AC: 2951 AN: 10518

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24721 AN: 67892

Other (OTH) AF: 0.438 AC: 922 AN: 2104

Alfa AF: 0.403 Hom.: 35376

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
PhyloP100		-0.049

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: rs7575835; hg19: chr2-110980346;