dbSNP rs963000489: UNCX:p.Gly258Glu (chr7-1236154-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001080461.3(UNCX):c.773G>A(p.Gly258Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,228,494 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

UNCX
NM_001080461.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1904602).

BS2

High AC in GnomAd4 at 8 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.773G>A	p.Gly258Glu	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.773G>A	p.Gly258Glu	missense	Exon 3 of 3	ENSP00000314480.8	A6NJT0

Frequencies

GnomAD3 genomes

AF:

0.0000544

AC:

AN:

147114

Hom.:

Cov.:

show subpopulations

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:

0.000121

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

9010

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:

0.0000620

AC:

AN:

1081380

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

523288

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

20588

American (AMR)

AF:

0.000148

AC:

AN:

6768

Ashkenazi Jewish (ASJ)

AF:

0.0000850

AC:

AN:

11766

East Asian (EAS)

AF:

0.00

AC:

AN:

20002

South Asian (SAS)

AF:

0.00

AC:

AN:

34412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2632

European-Non Finnish (NFE)

AF:

0.0000678

AC:

AN:

915024

Other (OTH)

AF:

0.0000491

AC:

AN:

40696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000544

AC:

AN:

147114

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

71588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40658

American (AMR)

AF:

0.00

AC:

AN:

14876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4972

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.000121

AC:

AN:

66184

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000142

Hom.:

Bravo

AF:

0.0000378

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

0.15

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.085

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.4

PhyloP100

2.2

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Benign

0.12

Polyphen

0.047

Vest4

0.21

MutPred

0.31

Gain of helix (P = 0.0225)

MVP

0.30

ClinPred

0.18

GERP RS

3.4

Varity_R

0.16

gMVP

0.17

Mutation Taster

=94/6

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