4-95170263-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003728.4(UNC5C):c.2521G>A(p.Ala841Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,614,124 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 40 hom., cov: 32)

Exomes 𝑓: 0.020 ( 384 hom. )

Consequence

UNC5C
NM_003728.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.91

Publications

20 publications found

Variant links:

Genes affected

UNC5C (HGNC:12569): (unc-5 netrin receptor C) This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]

UNC5C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0082755685).

BP6

Variant 4-95170263-C-T is Benign according to our data. Variant chr4-95170263-C-T is described in ClinVar as [Benign]. Clinvar id is 2654955.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0174 (2649/152248) while in subpopulation EAS AF = 0.0418 (216/5162). AF 95% confidence interval is 0.0373. There are 40 homozygotes in GnomAd4. There are 1249 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4 link	c.2521G>A	p.Ala841Thr	missense_variant	Exon 15 of 16	ENST00000453304.6	NP_003719.3	O95185-1A8K385
UNC5C	XM_005263321.4 link	c.2578G>A	p.Ala860Thr	missense_variant	Exon 16 of 17		XP_005263378.1
UNC5C	XM_047416345.1 link	c.1477G>A	p.Ala493Thr	missense_variant	Exon 17 of 18		XP_047272301.1
UNC5C	XM_047416346.1 link	c.1477G>A	p.Ala493Thr	missense_variant	Exon 18 of 19		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6 link	c.2521G>A	p.Ala841Thr	missense_variant	Exon 15 of 16	1	NM_003728.4	ENSP00000406022.1		O95185-1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2635

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.0419

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0320

GnomAD2 exomes

AF:

0.0199

AC:

5003

AN:

251442

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0537

Gnomad EAS exome

AF:

0.0420

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0198

AC:

28935

AN:

1461876

Hom.:

384

Cov.:

AF XY:

0.0199

AC XY:

14443

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00544

AC:

182

AN:

33480

American (AMR)

AF:

0.0204

AC:

912

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

1416

AN:

26136

East Asian (EAS)

AF:

0.0409

AC:

1623

AN:

39700

South Asian (SAS)

AF:

0.0159

AC:

1368

AN:

86256

European-Finnish (FIN)

AF:

0.00270

AC:

144

AN:

53418

Middle Eastern (MID)

AF:

0.0352

AC:

203

AN:

5764

European-Non Finnish (NFE)

AF:

0.0194

AC:

21578

AN:

1112008

Other (OTH)

AF:

0.0250

AC:

1509

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1711

3421

5132

6842

8553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.0174

AC:

2649

AN:

152248

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1249

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00556

AC:

231

AN:

41550

American (AMR)

AF:

0.0332

AC:

508

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0533

AC:

185

AN:

3468

East Asian (EAS)

AF:

0.0418

AC:

216

AN:

5162

South Asian (SAS)

AF:

0.0185

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0191

AC:

1301

AN:

68008

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

126

252

378

504

630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0206

Hom.:

151

Bravo

AF:

0.0195

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0195

AC:

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.0201

AC:

173

ExAC

AF:

0.0186

AC:

2257

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

UNC5C: BS1, BS2 -

UNC5C-related disorder

Benign:1

Feb 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.9

.;M

PhyloP100

7.9

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.7

.;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

.;D

Sift4G

Benign

0.14

T;T

Polyphen

1.0

.;D

Vest4

0.30

MPC

0.82

ClinPred

0.017

GERP RS

5.5

Varity_R

0.51

gMVP

0.65

Mutation Taster

=87/13

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over