Genetic Variant NM_031944.3:c.76G>T (chr1-226223757-G-T) – 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.76G>T(p.Gly26Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,421,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

MIXL1
NM_031944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.476

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=0.22785112).

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.76G>T	p.Gly26Cys	missense	Exon 1 of 2	NP_114150.1	Q9H2W2-1
	MIXL1	NM_001282402.2		c.76G>T	p.Gly26Cys	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.76G>T	p.Gly26Cys	missense	Exon 1 of 2	ENSP00000355775.4	Q9H2W2-1
	MIXL1	ENST00000542034.5	TSL:1	c.76G>T	p.Gly26Cys	missense	Exon 1 of 2	ENSP00000442439.1	Q9H2W2-2

Frequencies

GnomAD3 genomes

AF:

0.0000728

AC:

AN:

151172

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000619

AC:

AN:

48440

AF XY:

0.0000359

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1270334

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

624544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25764

American (AMR)

AF:

0.00

AC:

AN:

22042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20756

East Asian (EAS)

AF:

0.00

AC:

AN:

27278

South Asian (SAS)

AF:

0.00

AC:

AN:

65268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.0000518

AC:

AN:

1022482

Other (OTH)

AF:

0.0000385

AC:

AN:

51890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000728

AC:

AN:

151172

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41272

American (AMR)

AF:

0.00

AC:

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67752

Other (OTH)

AF:

0.00

AC:

AN:

2082

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

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

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

0.24

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.34

MutationAssessor

Benign

0.90

PhyloP100

-0.48

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

Sift4G

Benign

0.099

Polyphen

0.54

Vest4

0.10

MutPred

0.26

Loss of relative solvent accessibility (P = 0.0186)

MVP

0.38

MPC

0.85

ClinPred

0.17

GERP RS

-0.43

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.18

gMVP

0.47

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over