Variant 7-157005528-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005515.4(MNX1):c.1198C>T(p.Pro400Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,359,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

MNX1
NM_005515.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

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]

MNX1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2875637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	3/3	ENST00000252971.11	NP_005506.3	P50219-1
MNX1	NM_001165255.2 linkuse as main transcript	c.562C>T	p.Pro188Ser	missense_variant	3/3		NP_001158727.1	P50219-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MNX1	ENST00000252971.11 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	3/3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1	ENST00000543409.5 linkuse as main transcript	c.562C>T	p.Pro188Ser	missense_variant	3/3	1		ENSP00000438552.1	P50219-2
MNX1	ENST00000469500.5 linkuse as main transcript	c.55+3470C>T		intron_variant		1		ENSP00000475129.1	S4R464
MNX1	ENST00000479817.1 linkuse as main transcript	c.37+4132C>T		intron_variant		1		ENSP00000474286.1	S4R3G1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000860

AC:

AN:

116262

Hom.:

AF XY:

0.00

AC XY:

AN XY:

64612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000298

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1359924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670950

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:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Currarino triad

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.39

T;T

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0080

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.035

.;B

Vest4

0.15

MutPred

0.27

.;Gain of phosphorylation at P400 (P = 0.0067);

MVP

0.46

ClinPred

0.37

GERP RS

2.2

Varity_R

0.10

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over