Variant 1-226223743-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000366810.6(MIXL1):c.62G>C(p.Arg21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000728 in 1,442,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

MIXL1
ENST00000366810.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.446

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14344743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3 linkuse as main transcript	c.62G>C	p.Arg21Pro	missense_variant	1/2	ENST00000366810.6	NP_114150.1
MIXL1	NM_001282402.2 linkuse as main transcript	c.62G>C	p.Arg21Pro	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.62G>C	p.Arg21Pro	missense_variant	1/2	1	NM_031944.3	ENSP00000355775	P1	Q9H2W2-1
MIXL1	ENST00000542034.5 linkuse as main transcript	c.62G>C	p.Arg21Pro	missense_variant	1/2	1		ENSP00000442439		Q9H2W2-2

Frequencies

GnomAD3 genomes

AF:

0.0000595

AC:

AN:

151340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000154

AC:

AN:

64948

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

37266

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:

0.0000429

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000743

AC:

AN:

1291434

Hom.:

Cov.:

AF XY:

0.0000723

AC XY:

AN XY:

636052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000362

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000909

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.0000595

AC:

AN:

151340

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73924

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

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

Nov 09, 2021

The c.62G>C (p.R21P) alteration is located in exon 1 (coding exon 1) of the MIXL1 gene. This alteration results from a G to C substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a proline (P). 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

0.074

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.8

DANN

Benign

0.78

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.45

T;T

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.95

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.33

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0

.;B

Vest4

0.10

MutPred

0.28

Loss of methylation at R21 (P = 0.0266);Loss of methylation at R21 (P = 0.0266);

MVP

0.31

MPC

0.74

ClinPred

0.030

GERP RS

-0.67

Varity_R

0.14

gMVP

0.32

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