Genetic Variant NM_001080461.3:c.628A>C (chr7-1236009-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.628A>C(p.Lys210Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,455,630 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: not found (cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

UNCX
NM_001080461.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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=0.3811953).

BS2

High AC in GnomAdExome4 at 56 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.628A>C	p.Lys210Gln	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.628A>C	p.Lys210Gln	missense	Exon 3 of 3	ENSP00000314480.8	A6NJT0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000131

AC:

AN:

229464

AF XY:

0.0000158

show subpopulations

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:

0.0000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

1455630

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

723760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.0000468

AC:

AN:

1110112

Other (OTH)

AF:

0.0000500

AC:

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000832

AC:

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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.1

PhyloP100

1.2

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.31

Sift

Uncertain

0.011

Sift4G

Benign

0.11

Polyphen

0.90

Vest4

0.14

MutPred

0.23

Loss of methylation at K210 (P = 0.0079)

MVP

0.62

ClinPred

0.32

GERP RS

3.9

Varity_R

0.26

gMVP

0.52

Mutation Taster

=81/19

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over