Variant 1-226225713-A-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.600A>C(p.Gln200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

MIXL1
ENST00000366810.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.246

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=0.083998114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3 linkuse as main transcript	c.600A>C	p.Gln200His	missense_variant	2/2	ENST00000366810.6	NP_114150.1
MIXL1	NM_001282402.2 linkuse as main transcript	c.624A>C	p.Gln208His	missense_variant	2/2		NP_001269331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6 linkuse as main transcript	c.600A>C	p.Gln200His	missense_variant	2/2	1	NM_031944.3	ENSP00000355775	P1	Q9H2W2-1
MIXL1	ENST00000542034.5 linkuse as main transcript	c.624A>C	p.Gln208His	missense_variant	2/2	1		ENSP00000442439		Q9H2W2-2
MIXL1	ENST00000557734.1 linkuse as main transcript	n.146-38A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

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:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251302

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000719

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000367

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000123

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Apr 17, 2024

The c.600A>C (p.Q200H) alteration is located in exon 2 (coding exon 2) of the MIXL1 gene. This alteration results from a A to C substitution at nucleotide position 600, causing the glutamine (Q) at amino acid position 200 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.15

Sift

Benign

0.094

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.98

.;D

Vest4

0.25

MutPred

0.18

.;Loss of solvent accessibility (P = 0.0576);

MVP

0.36

MPC

1.3

ClinPred

0.21

GERP RS

0.55

Varity_R

0.073

gMVP

0.43

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