1-226223851-G-C

Position:

• chr1-226223851-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000366810.6(MIXL1):​c.170G>C​(p.Gly57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MIXL1 ENST00000366810.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0390

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]

ACMG classification

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=0.19431755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3	c.170G>C	p.Gly57Ala	missense_variant	1/2	ENST00000366810.6	NP_114150.1
MIXL1	NM_001282402.2	c.170G>C	p.Gly57Ala	missense_variant	1/2		NP_001269331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6	c.170G>C	p.Gly57Ala	missense_variant	1/2	1	NM_031944.3	ENSP00000355775	P1
MIXL1	ENST00000542034.5	c.170G>C	p.Gly57Ala	missense_variant	1/2	1		ENSP00000442439

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.170G>C (p.G57A) alteration is located in exon 1 (coding exon 1) of the MIXL1 gene. This alteration results from a G to C substitution at nucleotide position 170, causing the glycine (G) at amino acid position 57 to be replaced by an alanine (A). 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	0.10
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.7
DANN	Benign	0.84
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.50	T;T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.37	T;T
Polyphen		0.13	.;B
Vest4		0.053
MutPred		0.14		Gain of glycosylation at P62 (P = 0.1504);Gain of glycosylation at P62 (P = 0.1504);
MVP		0.68
MPC		0.55
ClinPred		0.062	T
GERP RS		1.6
Varity_R		0.080
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-226411552;