7-1236216-G-A

Variant names:

• chr7-1236216-G-A
• rs1288598830
• NM_001080461.3:c.835G>A

Variant summary

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

The NM_001080461.3(UNCX):​c.835G>A​(p.Gly279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000298 in 1,344,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G279R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: UNCX NM_001080461.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 0 publications found

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

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=0.14061677).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080461.3. 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
	UNCX	NM_001080461.3	MANE Select	c.835G>A	p.Gly279Ser	missense	Exon 3 of 3	NP_001073930.1	A6NJT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNCX	ENST00000316333.9	TSL:1 MANE Select	c.835G>A	p.Gly279Ser	missense	Exon 3 of 3	ENSP00000314480.8	A6NJT0

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148346 Hom.: 0 Cov.: 32

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: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000167 AC: 2 AN: 1196020 Hom.: 0 Cov.: 31 AF XY: 0.00000170 AC XY: 1 AN XY: 589910

African (AFR) AF: 0.00 AC: 0 AN: 23178

American (AMR) AF: 0.00 AC: 0 AN: 21754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18342

East Asian (EAS) AF: 0.00 AC: 0 AN: 19358

South Asian (SAS) AF: 0.00 AC: 0 AN: 66644

European-Finnish (FIN) AF: 0.0000370 AC: 1 AN: 26996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3210

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 970692

Other (OTH) AF: 0.00 AC: 0 AN: 45846

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148346 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72264

African (AFR) AF: 0.00 AC: 0 AN: 40918

American (AMR) AF: 0.00 AC: 0 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000300 AC: 2 AN: 66700

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.73
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.11
Sift	Benign	0.091	T
Sift4G	Benign	0.37	T
Polyphen		0.17	B
Vest4		0.16
MutPred		0.20		Gain of glycosylation at G279 (P = 0.0015)
MVP		0.29
ClinPred		0.063	T
GERP RS		3.4
Varity_R		0.11
gMVP		0.20
Mutation Taster		=91/9	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: rs1288598830; hg19: chr7-1275852;