Variant 1-226223773-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000366810.6(MIXL1):c.92C>A(p.Pro31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MIXL1
ENST00000366810.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0710

Variant links:

Genes affected

MIXL1 (HGNC:13363): (Mix paired-like homeobox) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including endodermal cell differentiation; hematopoietic progenitor cell differentiation; and positive regulation of mesoderm development. Predicted to act upstream of or within cell migration involved in gastrulation and hemopoiesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIXL1 links:

Genome browser will be placed here

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=0.2867484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/2	ENST00000366810.6	NP_114150.1
MIXL1	NM_001282402.2 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/2		NP_001269331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/2	1	NM_031944.3	ENSP00000355775	P1	Q9H2W2-1
MIXL1	ENST00000542034.5 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/2	1		ENSP00000442439		Q9H2W2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1246338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

611764

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:

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.92C>A (p.P31Q) alteration is located in exon 1 (coding exon 1) of the MIXL1 gene. This alteration results from a C to A substitution at nucleotide position 92, causing the proline (P) at amino acid position 31 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.48

.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.49

T;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

0.96

.;D

Vest4

0.19

MutPred

0.29

Loss of glycosylation at P31 (P = 0.0118);Loss of glycosylation at P31 (P = 0.0118);

MVP

0.72

MPC

1.3

ClinPred

0.63

GERP RS

1.6

Varity_R

0.079

gMVP

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over