chr1-226223832-A-C

Position:

• chr1-226223832-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000366810.6(MIXL1):​c.151A>C​(p.Thr51Pro) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIXL1 ENST00000366810.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04999873).
• BP6: Variant 1-226223832-A-C is Benign according to our data. Variant chr1-226223832-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2250208.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIXL1	NM_031944.3	c.151A>C	p.Thr51Pro	missense_variant	1/2	ENST00000366810.6	NP_114150.1
MIXL1	NM_001282402.2	c.151A>C	p.Thr51Pro	missense_variant	1/2		NP_001269331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIXL1	ENST00000366810.6	c.151A>C	p.Thr51Pro	missense_variant	1/2	1	NM_031944.3	ENSP00000355775	P1
MIXL1	ENST00000542034.5	c.151A>C	p.Thr51Pro	missense_variant	1/2	1		ENSP00000442439

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.2
DANN	Benign	0.61
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.17	T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.55	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.15
Sift	Benign	0.26	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	.;B
Vest4		0.059
MutPred		0.19		Loss of phosphorylation at T51 (P = 0.0108);Loss of phosphorylation at T51 (P = 0.0108);
MVP		0.17
MPC		0.66
ClinPred		0.32	T
GERP RS		-7.4
Varity_R		0.098
gMVP		0.35

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: chr1-226411533;