7-157005556-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005515.4(MNX1):​c.1170G>A​(p.Pro390Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MNX1
NM_005515.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41
Variant links:
Genes affected
MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 7-157005556-C-T is Benign according to our data. Variant chr7-157005556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3658001.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.41 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MNX1NM_005515.4 linkc.1170G>A p.Pro390Pro synonymous_variant Exon 3 of 3 ENST00000252971.11 NP_005506.3 P50219-1
MNX1NM_001165255.2 linkc.534G>A p.Pro178Pro synonymous_variant Exon 3 of 3 NP_001158727.1 P50219-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MNX1ENST00000252971.11 linkc.1170G>A p.Pro390Pro synonymous_variant Exon 3 of 3 1 NM_005515.4 ENSP00000252971.5 P50219-1
MNX1ENST00000543409.5 linkc.534G>A p.Pro178Pro synonymous_variant Exon 3 of 3 1 ENSP00000438552.1 P50219-2
MNX1ENST00000469500.5 linkc.55+3442G>A intron_variant Intron 1 of 1 1 ENSP00000475129.1 S4R464
MNX1ENST00000479817.1 linkc.37+4104G>A intron_variant Intron 1 of 1 1 ENSP00000474286.1 S4R3G1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.13e-7
AC:
1
AN:
1402060
Hom.:
0
Cov.:
31
AF XY:
0.00000144
AC XY:
1
AN XY:
694410
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.20e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 14, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
11
DANN
Benign
0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-156798250; API