NM_145808.4:c.*1412C>T

Variant names:

• chr7-135928514-G-A
• rs17168525
• NM_145808.4:c.*1412C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPN	NM_145808.4	MANE Select	c.*1412C>T		3_prime_UTR	Exon 4 of 4	NP_665807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTPN	ENST00000393085.4	TSL:1 MANE Select	c.*1412C>T		3_prime_UTR	Exon 4 of 4	ENSP00000376800.3
	ENSG00000224746	ENST00000419211.3	TSL:2	n.891+1929G>A		intron	N/A
	ENSG00000224746	ENST00000830862.1		n.738+1929G>A		intron	N/A

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0423 AC: 622 AN: 14690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 84

Other (OTH) AF: 0.0222 AC: 2 AN: 90

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

African (AFR) AF: 0.00733 AC: 304 AN: 41468

American (AMR) AF: 0.0157 AC: 240 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3466

East Asian (EAS) AF: 0.178 AC: 920 AN: 5166

South Asian (SAS) AF: 0.0451 AC: 217 AN: 4814

European-Finnish (FIN) AF: 0.0394 AC: 417 AN: 10572

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00600 AC: 408 AN: 67962

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs17168525; hg19: chr7-135613262;