Variant 1-226223871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031944.3(MIXL1):c.190C>T(p.Pro64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00034 in 1,204,256 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 8 hom. )

Consequence

MIXL1
NM_031944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.775

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017288268).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3 linkuse as main transcript	c.190C>T	p.Pro64Ser	missense_variant	1/2	ENST00000366810.6	NP_114150.1	Q9H2W2-1A0A024R3T7
MIXL1	NM_001282402.2 linkuse as main transcript	c.190C>T	p.Pro64Ser	missense_variant	1/2		NP_001269331.1	Q9H2W2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6 linkuse as main transcript	c.190C>T	p.Pro64Ser	missense_variant	1/2	1	NM_031944.3	ENSP00000355775.4		Q9H2W2-1
MIXL1	ENST00000542034.5 linkuse as main transcript	c.190C>T	p.Pro64Ser	missense_variant	1/2	1		ENSP00000442439.1		Q9H2W2-2

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

150534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0107

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000603

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000741

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000666

AC:

AN:

1502

Hom.:

AF XY:

0.00

AC XY:

AN XY:

982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00146

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000309

AC:

326

AN:

1053614

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

163

AN XY:

500762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00673

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.000673

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.000973

GnomAD4 genome

AF:

0.000558

AC:

AN:

150642

Hom.:

Cov.:

AF XY:

0.000693

AC XY:

AN XY:

73606

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0111

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000603

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.000801

ExAC

AF:

0.000336

AC:

Asia WGS

AF:

0.00651

AC:

AN:

3396

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

Jun 22, 2021

The c.190C>T (p.P64S) alteration is located in exon 1 (coding exon 1) of the MIXL1 gene. This alteration results from a C to T substitution at nucleotide position 190, causing the proline (P) at amino acid position 64 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.2

DANN

Benign

0.97

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

T;T

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.90

N;N

REVEL

Benign

0.17

Sift

Benign

0.33

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0

.;B

Vest4

0.16

MutPred

0.26

Gain of phosphorylation at P64 (P = 0.0031);Gain of phosphorylation at P64 (P = 0.0031);

MVP

0.22

MPC

0.51

ClinPred

0.023

GERP RS

-2.1

Varity_R

0.019

gMVP

0.42

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