Variant 7-157005549-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005515.4(MNX1):c.1177C>G(p.Arg393Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000518 in 1,544,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MNX1
NM_005515.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29030925).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.1177C>G	p.Arg393Gly	missense_variant	3/3	ENST00000252971.11	NP_005506.3	P50219-1
MNX1	NM_001165255.2 linkuse as main transcript	c.541C>G	p.Arg181Gly	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.1177C>G	p.Arg393Gly	missense_variant	3/3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1	ENST00000543409.5 linkuse as main transcript	c.541C>G	p.Arg181Gly	missense_variant	3/3	1		ENSP00000438552.1	P50219-2
MNX1	ENST00000469500.5 linkuse as main transcript	c.55+3449C>G		intron_variant		1		ENSP00000475129.1	S4R464
MNX1	ENST00000479817.1 linkuse as main transcript	c.37+4111C>G		intron_variant		1		ENSP00000474286.1	S4R3G1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1392542

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689066

show subpopulations

Gnomad4 AFR exome

AF:

0.0000692

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Jun 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.44

T;T

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.26

Sift

Benign

0.30

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.98

.;D

Vest4

0.17

MutPred

0.19

.;Gain of glycosylation at S395 (P = 0.0849);

MVP

0.62

ClinPred

0.22

GERP RS

-2.4

Varity_R

0.16

gMVP

0.27

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