4-95169241-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003728.4(UNC5C):c.2789A>G(p.Gln930Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UNC5C NM_003728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66

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]

ACMG classification

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=0.25891787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.2789A>G	p.Gln930Arg	missense_variant	16/16	ENST00000453304.6
UNC5C	XM_005263321.4	c.2846A>G	p.Gln949Arg	missense_variant	17/17
UNC5C	XM_047416345.1	c.1745A>G	p.Gln582Arg	missense_variant	18/18
UNC5C	XM_047416346.1	c.1745A>G	p.Gln582Arg	missense_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.2789A>G	p.Gln930Arg	missense_variant	16/16	1	NM_003728.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2022

The c.2789A>G (p.Q930R) alteration is located in exon 16 (coding exon 16) of the UNC5C gene. This alteration results from a A to G substitution at nucleotide position 2789, causing the glutamine (Q) at amino acid position 930 to be replaced by an arginine (R). 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	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.54	D
PrimateAI	Uncertain	0.56	T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.0020	.;B
Vest4		0.20
MutPred		0.24		.;Gain of methylation at Q930 (P = 0.0422);
MVP		0.79
MPC		0.24
ClinPred		0.50	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-96090392;