Genetic Variant MIXL1:p.Pro65Gln (chr1-226223875-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031944.3(MIXL1):c.194C>A(p.Pro65Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MIXL1
NM_031944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2223019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	NM_031944.3	MANE Select	c.194C>A	p.Pro65Gln	missense	Exon 1 of 2	NP_114150.1	Q9H2W2-1
	MIXL1	NM_001282402.2		c.194C>A	p.Pro65Gln	missense	Exon 1 of 2	NP_001269331.1	Q9H2W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	ENST00000366810.6	TSL:1 MANE Select	c.194C>A	p.Pro65Gln	missense	Exon 1 of 2	ENSP00000355775.4	Q9H2W2-1
	MIXL1	ENST00000542034.5	TSL:1	c.194C>A	p.Pro65Gln	missense	Exon 1 of 2	ENSP00000442439.1	Q9H2W2-2

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1061016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

504556

African (AFR)

AF:

0.00

AC:

AN:

21736

American (AMR)

AF:

0.00

AC:

AN:

7526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12770

East Asian (EAS)

AF:

0.00

AC:

AN:

23716

South Asian (SAS)

AF:

0.00

AC:

AN:

20082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

908666

Other (OTH)

AF:

0.00

AC:

AN:

41670

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150722

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41266

American (AMR)

AF:

0.00

AC:

AN:

15116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67598

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

7.2

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.27

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.30

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.22

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.50

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.095

Polyphen

0.0060

Vest4

0.17

MutPred

0.27

Loss of glycosylation at P65 (P = 0.0018)

MVP

0.28

MPC

0.47

ClinPred

0.041

GERP RS

-4.5

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.029

gMVP

0.45

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over