chr1-226223698-C-T

Variant names:

• chr1-226223698-C-T
• rs2102809343
• NM_031944.3:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031944.3(MIXL1):​c.17C>T​(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MIXL1 NM_031944.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24576163).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	NM_031944.3	MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 2	NP_114150.1	Q9H2W2-1
	MIXL1	NM_001282402.2		c.17C>T	p.Ser6Phe	missense	Exon 1 of 2	NP_001269331.1	Q9H2W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	ENST00000366810.6	TSL:1 MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 2	ENSP00000355775.4	Q9H2W2-1
	MIXL1	ENST00000542034.5	TSL:1	c.17C>T	p.Ser6Phe	missense	Exon 1 of 2	ENSP00000442439.1	Q9H2W2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320652 Hom.: 0 Cov.: 32 AF XY: 0.00000153 AC XY: 1 AN XY: 653188

African (AFR) AF: 0.00 AC: 0 AN: 26906

American (AMR) AF: 0.00 AC: 0 AN: 27510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22554

East Asian (EAS) AF: 0.00 AC: 0 AN: 28796

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 71156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051848

Other (OTH) AF: 0.00 AC: 0 AN: 54244

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.024	D
Polyphen		0.74	P
Vest4		0.24
MutPred		0.25		Gain of catalytic residue at S6 (P = 0.0196)
MVP		0.72
MPC		1.3
ClinPred		0.51	D
GERP RS		3.2
PromoterAI		0.0089	Neutral
Varity_R		0.088
gMVP		0.31
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2102809343; hg19: chr1-226411399;