7-1234209-A-T

Variant names:

• chr7-1234209-A-T
• rs10275044
• NM_001080461.3:c.450+514A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080461.3(UNCX):​c.450+514A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,230 control chromosomes in the GnomAD database, including 32,949 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (32949 hom., cov: 33)
• Consequence: UNCX NM_001080461.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNCX	NM_001080461.3	c.450+514A>T		intron_variant	Intron 2 of 2	ENST00000316333.9	NP_001073930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNCX	ENST00000316333.9	c.450+514A>T		intron_variant	Intron 2 of 2	1	NM_001080461.3	ENSP00000314480.8

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92341 AN: 152112 Hom.: 32944 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.607 AC: 92355 AN: 152230 Hom.: 32949 Cov.: 33 AF XY: 0.607 AC XY: 45154 AN XY: 74440

African (AFR) AF: 0.223 AC: 9240 AN: 41524

American (AMR) AF: 0.702 AC: 10742 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2683 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1802 AN: 5180

South Asian (SAS) AF: 0.699 AC: 3379 AN: 4832

European-Finnish (FIN) AF: 0.762 AC: 8080 AN: 10602

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54391 AN: 68008

Other (OTH) AF: 0.608 AC: 1285 AN: 2112

Alfa AF: 0.619 Hom.: 2432

Bravo AF: 0.581

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.59
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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: rs10275044; hg19: chr7-1273845;