1-226225724-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000366810.6(MIXL1):ā€‹c.611T>Cā€‹(p.Phe204Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,614,022 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000045 ( 0 hom. )

Consequence

MIXL1
ENST00000366810.6 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
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]

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=0.23309663).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MIXL1NM_031944.3 linkuse as main transcriptc.611T>C p.Phe204Ser missense_variant 2/2 ENST00000366810.6 NP_114150.1
MIXL1NM_001282402.2 linkuse as main transcriptc.635T>C p.Phe212Ser missense_variant 2/2 NP_001269331.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MIXL1ENST00000366810.6 linkuse as main transcriptc.611T>C p.Phe204Ser missense_variant 2/21 NM_031944.3 ENSP00000355775 P1Q9H2W2-1
MIXL1ENST00000542034.5 linkuse as main transcriptc.635T>C p.Phe212Ser missense_variant 2/21 ENSP00000442439 Q9H2W2-2
MIXL1ENST00000557734.1 linkuse as main transcriptn.146-27T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251108
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000451
AC:
66
AN:
1461816
Hom.:
0
Cov.:
31
AF XY:
0.0000468
AC XY:
34
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74360
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMay 11, 2022The c.611T>C (p.F204S) alteration is located in exon 2 (coding exon 2) of the MIXL1 gene. This alteration results from a T to C substitution at nucleotide position 611, causing the phenylalanine (F) at amino acid position 204 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
0.13
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
.;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
.;L
MutationTaster
Benign
0.61
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Benign
0.096
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.99
.;D
Vest4
0.55
MutPred
0.29
.;Loss of loop (P = 0.0112);
MVP
0.63
MPC
1.8
ClinPred
0.42
T
GERP RS
5.7
Varity_R
0.47
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs747359656; hg19: chr1-226413425; API