5-176874045-G-C

Position:

• chr5-176874045-G-C

Variant summary

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

The NM_133369.3(UNC5A):​c.964G>C​(p.Val322Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.75

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5A	NM_133369.3	c.964G>C	p.Val322Leu	missense_variant	7/15	ENST00000329542.9	NP_588610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5A	ENST00000329542.9	c.964G>C	p.Val322Leu	missense_variant	7/15	1	NM_133369.3	ENSP00000332737.4
UNC5A	ENST00000513890.1	n.*1016G>C		non_coding_transcript_exon_variant	8/9	1		ENSP00000424067.1
UNC5A	ENST00000513890.1	n.*1016G>C		3_prime_UTR_variant	8/9	1		ENSP00000424067.1
UNC5A	ENST00000509580.2	c.1132G>C	p.Val378Leu	missense_variant	8/16	5		ENSP00000421795.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Sep 22, 2023

The c.964G>C (p.V322L) alteration is located in exon 7 (coding exon 7) of the UNC5A gene. This alteration results from a G to C substitution at nucleotide position 964, causing the valine (V) at amino acid position 322 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.13
Sift	Benign	0.10	T;.
Sift4G	Uncertain	0.060	T;.
Polyphen		0.87	P;.
Vest4		0.54
MutPred		0.30		Gain of sheet (P = 0.0827);.;
MVP		0.54
MPC		1.0
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.72

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: chr5-176301046;