chr7-1233678-G-A

Position:

• chr7-1233678-G-A

Variant summary

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

The NM_001080461.3(UNCX):​c.433G>A​(p.Val145Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: UNCX NM_001080461.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77

Genes affected

UNCX (HGNC:33194): (UNC homeobox) This gene encodes a homeobox transcription factor that is involved in somitogenesis and neurogenesis and is required for the maintenance and differentiation of specific elements of the axial skeleton. This gene also plays a role in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and deliver hormones that control peripheral functions. The expression of this gene is associated with an increased frequency of acute myeloid leukemia. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNCX	NM_001080461.3	c.433G>A	p.Val145Ile	missense_variant	2/3	ENST00000316333.9	NP_001073930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNCX	ENST00000316333.9	c.433G>A	p.Val145Ile	missense_variant	2/3	1	NM_001080461.3	ENSP00000314480	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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

Jun 10, 2024

The c.433G>A (p.V145I) alteration is located in exon 2 (coding exon 2) of the UNCX gene. This alteration results from a G to A substitution at nucleotide position 433, causing the valine (V) at amino acid position 145 to be replaced by an isoleucine (I). 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	0.29
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.75	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.32
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.39	B
Vest4		0.17
MutPred		0.50		Loss of MoRF binding (P = 0.1286);
MVP		0.28
ClinPred		0.52	D
GERP RS		3.0
Varity_R		0.12
gMVP		0.78

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: chr7-1273314;