Genetic Variant NM_001080461.3:c.257A>C (chr7-1233274-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNCX	NM_001080461.3 link	c.257A>C	p.Gln86Pro	missense_variant	Exon 1 of 3	ENST00000316333.9	NP_001073930.1	A6NJT0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNCX	ENST00000316333.9 link	c.257A>C	p.Gln86Pro	missense_variant	Exon 1 of 3	1	NM_001080461.3	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

GnomAD4 exome

AF:

0.000226

AC:

266

AN:

1177432

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

128

AN XY:

569908

show subpopulations

Gnomad4 AFR exome

AF:

0.0000431

Gnomad4 AMR exome

AF:

0.000328

Gnomad4 ASJ exome

AF:

0.00201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.000438

GnomAD4 genome

AF:

0.000231

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000925

Hom.:

Bravo

AF:

0.000261

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.257A>C (p.Q86P) alteration is located in exon 1 (coding exon 1) of the UNCX gene. This alteration results from a A to C substitution at nucleotide position 257, causing the glutamine (Q) at amino acid position 86 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

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

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

Varity_R

0.62

gMVP

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over