rs17168525

Positions:

• chr7-135928514-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145808.4(MTPN):​c.*1412C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 166,926 control chromosomes in the GnomAD database, including 102 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 0.017 (94 hom., cov: 32)
  • Exomes 𝑓: 0.042 (8 hom.)
• Consequence: MTPN NM_145808.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

MTPN (HGNC:15667): (myotrophin) The transcript produced from this gene is bi-cistronic and can encode both myotrophin and leucine zipper protein 6. The myotrophin protein is associated with cardiac hypertrophy, where it is involved in the conversion of NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers. This protein also has a potential function in cerebellar morphogenesis, and it may be involved in the differentiation of cerebellar neurons, particularly of granule cells. A cryptic ORF at the 3' end of this transcript uses a novel internal ribosome entry site and a non-AUG translation initiation codon to produce leucine zipper protein 6, a 6.4 kDa tumor antigen that is associated with myeloproliferative disease. [provided by RefSeq, Jul 2008]

ENSG00000224746 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTPN	NM_145808.4	c.*1412C>T		3_prime_UTR_variant	4/4	ENST00000393085.4	NP_665807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTPN	ENST00000393085.4	c.*1412C>T		3_prime_UTR_variant	4/4	1	NM_145808.4	ENSP00000376800.3
ENSG00000224746	ENST00000419211.2	n.879+1929G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2553 AN: 151930 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0420 AC: 625 AN: 14878 Hom.: 8 Cov.: 0 AF XY: 0.0417 AC XY: 295 AN XY: 7066

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0168 AC: 2558 AN: 152048 Hom.: 94 Cov.: 32 AF XY: 0.0197 AC XY: 1465 AN XY: 74306

Gnomad4 AFR AF: 0.00733

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0451

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.00600

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00810 Hom.: 3

Bravo AF: 0.0153

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.91

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: rs17168525; hg19: chr7-135613262;