8-35722252-G-A

Position:

• chr8-35722252-G-A

Variant summary

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

The NM_080872.4(UNC5D):​c.1160G>A​(p.Gly387Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UNC5D NM_080872.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

Genes affected

UNC5D (HGNC:18634): (unc-5 netrin receptor D) Predicted to enable netrin receptor activity. Involved in cell-cell adhesion via plasma-membrane adhesion molecules. Predicted to be located in cell surface and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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	UniProt
UNC5D	NM_080872.4	c.1160G>A	p.Gly387Asp	missense_variant	9/17	ENST00000404895.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5D	ENST00000404895.7	c.1160G>A	p.Gly387Asp	missense_variant	9/17	1	NM_080872.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Feb 28, 2024

The c.1160G>A (p.G387D) alteration is located in exon 9 (coding exon 9) of the UNC5D gene. This alteration results from a G to A substitution at nucleotide position 1160, causing the glycine (G) at amino acid position 387 to be replaced by an aspartic acid (D). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;T;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.9	M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.062	T;T;T;T;T
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		1.0	D;.;.;D;D
Vest4		0.79
MutPred		0.59		.;.;.;Gain of sheet (P = 0.0043);.;
MVP		0.37
MPC		1.1
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.85

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: chr8-35579770;