dbSNP rs17168525: MTPN:c.*1412C>T (chr7-135928514-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

7 publications found

Variant links:

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]

MTPN links:

ENSG00000224746 (HGNC:):

ENSG00000224746 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTPN	NM_145808.4 link	c.*1412C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000393085.4	NP_665807.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MTPN	ENST00000393085.4 link	c.*1412C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_145808.4	ENSP00000376800.3
ENSG00000224746	ENST00000419211.3 link	n.891+1929G>A	intron_variant	Intron 2 of 2	2
ENSG00000224746	ENST00000830862.1 link	n.738+1929G>A	intron_variant	Intron 2 of 2
ENSG00000224746	ENST00000830863.1 link	n.860+1929G>A	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2553

AN:

151930

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0417

AC XY:

295

AN XY:

7066

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0423

AC:

622

AN:

14690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.0222

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0168

AC:

2558

AN:

152048

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1465

AN XY:

74306

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.00600

AC:

408

AN:

67962

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00810

Hom.:

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

(source)

DANN

Benign

0.91

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over