dbSNP rs915335444: MIXL1:p.Ala50Glu (chr1-226223830-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.149C>A(p.Ala50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,210,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MIXL1
NM_031944.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

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=0.14208552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIXL1	NM_031944.3 link	c.149C>A	p.Ala50Glu	missense_variant	Exon 1 of 2	ENST00000366810.6	NP_114150.1	Q9H2W2-1A0A024R3T7
MIXL1	NM_001282402.2 link	c.149C>A	p.Ala50Glu	missense_variant	Exon 1 of 2		NP_001269331.1	Q9H2W2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6 link	c.149C>A	p.Ala50Glu	missense_variant	Exon 1 of 2	1	NM_031944.3	ENSP00000355775.4		Q9H2W2-1
MIXL1	ENST00000542034.5 link	c.149C>A	p.Ala50Glu	missense_variant	Exon 1 of 2	1		ENSP00000442439.1		Q9H2W2-2

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150254

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

AF:

0.00000754

AC:

AN:

1060308

Hom.:

Cov.:

AF XY:

0.00000395

AC XY:

AN XY:

506078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21424

American (AMR)

AF:

0.00

AC:

AN:

7964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12584

East Asian (EAS)

AF:

0.00

AC:

AN:

22546

South Asian (SAS)

AF:

0.00

AC:

AN:

22704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2956

European-Non Finnish (NFE)

AF:

0.00000880

AC:

AN:

908622

Other (OTH)

AF:

0.00

AC:

AN:

41152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73456

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67454

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.37

T;T

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.69

N;N

PhyloP100

-1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.077

Sift

Benign

0.041

D;D

Sift4G

Benign

1.0

T;T

Polyphen

0.25

.;B

Vest4

0.075

MutPred

0.28

Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);

MVP

0.48

MPC

1.5

ClinPred

0.50

GERP RS

2.8

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.064

gMVP

0.43

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over