Genetic Variant UNCX:p.Gln86Pro (chr7-1233274-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001080461.3(UNCX):c.257A>C(p.Gln86Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000226 in 1,329,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

UNCX
NM_001080461.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Publications

0 publications found

Variant links:

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]

UNCX links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30625027).

BS2

High AC in GnomAd4 at 35 AD gene.

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.257A>C	p.Gln86Pro	missense	Exon 1 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.257A>C	p.Gln86Pro	missense	Exon 1 of 3	ENSP00000314480.8	A6NJT0

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

151634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

4506

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000226

AC:

266

AN:

1177432

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

128

AN XY:

569908

show subpopulations

African (AFR)

AF:

0.0000431

AC:

AN:

23192

American (AMR)

AF:

0.000328

AC:

AN:

9144

Ashkenazi Jewish (ASJ)

AF:

0.00201

AC:

AN:

15938

East Asian (EAS)

AF:

0.00

AC:

AN:

26350

South Asian (SAS)

AF:

0.0000222

AC:

AN:

44994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.000212

AC:

208

AN:

978886

Other (OTH)

AF:

0.000438

AC:

AN:

47932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000231

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41444

American (AMR)

AF:

0.000459

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000251

AC:

AN:

67834

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000925

Hom.:

Bravo

AF:

0.000261

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.15

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.050

MutationAssessor

Benign

1.5

PhyloP100

4.3

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.45

Sift

Uncertain

0.012

Sift4G

Benign

0.26

Polyphen

0.87

Vest4

0.33

MutPred

0.31

Gain of catalytic residue at Q86 (P = 0.0197)

MVP

0.45

ClinPred

0.79

GERP RS

1.6

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.62

gMVP

0.77

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over