chr5-176870517-G-C

Position:

• chr5-176870517-G-C

Variant summary

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

The NM_133369.3(UNC5A):​c.869G>C​(p.Ser290Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: UNC5A NM_133369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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]

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=0.16835001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5A	NM_133369.3	c.869G>C	p.Ser290Thr	missense_variant	6/15	ENST00000329542.9	NP_588610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5A	ENST00000329542.9	c.869G>C	p.Ser290Thr	missense_variant	6/15	1	NM_133369.3	ENSP00000332737.4
UNC5A	ENST00000513890.1	n.*921G>C		non_coding_transcript_exon_variant	7/9	1		ENSP00000424067.1
UNC5A	ENST00000513890.1	n.*921G>C		3_prime_UTR_variant	7/9	1		ENSP00000424067.1
UNC5A	ENST00000509580.2	c.1037G>C	p.Ser346Thr	missense_variant	7/16	5		ENSP00000421795.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.083	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.045	N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.25
Sift	Benign	0.048	D;.
Sift4G	Uncertain	0.056	T;.
Polyphen		0.94	P;.
Vest4		0.18
MutPred		0.42		Loss of sheet (P = 0.0084);.;
MVP		0.34
MPC		0.77
ClinPred		0.23	T
GERP RS		3.7
Varity_R		0.060
gMVP		0.73

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

Other links and lift over

dbSNP: rs1758083899; hg19: chr5-176297518;