Variant 5-176868807-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133369.3(UNC5A):c.564C>G(p.Asp188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UNC5A
NM_133369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524

Variant links:

Genes affected

UNC5A (HGNC:12567): (unc-5 netrin receptor A) UNC5A belongs to a family of netrin-1 (MIM 601614) receptors thought to mediate the chemorepulsive effect of netrin-1 on specific axons. For more information on UNC5 proteins, see UNC5C (MIM 603610).[supplied by OMIM, Apr 2004]

UNC5A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09526503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5A	NM_133369.3 linkuse as main transcript	c.564C>G	p.Asp188Glu	missense_variant	5/15	ENST00000329542.9	NP_588610.2	Q6ZN44-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UNC5A	ENST00000329542.9 linkuse as main transcript	c.564C>G	p.Asp188Glu	missense_variant	5/15	1	NM_133369.3	ENSP00000332737.4	Q6ZN44-1
UNC5A	ENST00000513890.1 linkuse as main transcript	n.*616C>G		non_coding_transcript_exon_variant	6/9	1		ENSP00000424067.1	H0Y9G2
UNC5A	ENST00000513890.1 linkuse as main transcript	n.*616C>G		3_prime_UTR_variant	6/9	1		ENSP00000424067.1	H0Y9G2
UNC5A	ENST00000509580.2 linkuse as main transcript	c.564C>G	p.Asp188Glu	missense_variant	5/16	5		ENSP00000421795.2	H0Y8R2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451802

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.564C>G (p.D188E) alteration is located in exon 5 (coding exon 5) of the UNC5A gene. This alteration results from a C to G substitution at nucleotide position 564, causing the aspartic acid (D) at amino acid position 188 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.89

N;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.52

N;.

REVEL

Benign

0.12

Sift

Benign

1.0

T;.

Sift4G

Benign

0.92

T;.

Polyphen

0.0010

B;.

Vest4

0.21

MutPred

0.26

Gain of disorder (P = 0.1129);Gain of disorder (P = 0.1129);

MVP

0.19

MPC

0.56

ClinPred

0.46

GERP RS

4.5

Varity_R

0.36

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over