chr8-35568107-T-G

Position:

• chr8-35568107-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_080872.4(UNC5D):​c.332T>G​(p.Val111Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: UNC5D NM_080872.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.19

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5D	NM_080872.4	c.332T>G	p.Val111Gly	missense_variant	3/17	ENST00000404895.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5D	ENST00000404895.7	c.332T>G	p.Val111Gly	missense_variant	3/17	1	NM_080872.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461852 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

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

Oct 10, 2023

The c.332T>G (p.V111G) alteration is located in exon 3 (coding exon 3) of the UNC5D gene. This alteration results from a T to G substitution at nucleotide position 332, causing the valine (V) at amino acid position 111 to be replaced by a glycine (G). 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	0.71
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.42	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.012	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.65	P;.;.;.;P
Vest4		0.52
MutPred		0.59		Gain of disorder (P = 0.0146);Gain of disorder (P = 0.0146);Gain of disorder (P = 0.0146);Gain of disorder (P = 0.0146);.;
MVP		0.23
MPC		0.92
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.65
gMVP		0.78

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: rs1300883150; hg19: chr8-35425625; COSMIC: COSV105848255;