8-35360913-C-T

Variant names:

• chr8-35360913-C-T
• rs10503978
• NM_080872.4:c.103+125026C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080872.4(UNC5D):​c.103+125026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 152,204 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.012 (65 hom., cov: 32)
• Consequence: UNC5D NM_080872.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5D	NM_080872.4	c.103+125026C>T		intron_variant	Intron 1 of 16	ENST00000404895.7	NP_543148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5D	ENST00000404895.7	c.103+125026C>T		intron_variant	Intron 1 of 16	1	NM_080872.4	ENSP00000385143.2
UNC5D	ENST00000416672.5	c.103+125026C>T		intron_variant	Intron 1 of 17	5		ENSP00000412652.1
UNC5D	ENST00000420357.5	c.103+125026C>T		intron_variant	Intron 1 of 14	5		ENSP00000392739.1
UNC5D	ENST00000287272.6	c.103+125026C>T		intron_variant	Intron 1 of 15	5		ENSP00000287272.2

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1782 AN: 152086 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.0124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0118 AC: 1792 AN: 152204 Hom.: 65 Cov.: 32 AF XY: 0.0131 AC XY: 972 AN XY: 74404

African (AFR) AF: 0.00376 AC: 156 AN: 41528

American (AMR) AF: 0.0621 AC: 949 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5168

South Asian (SAS) AF: 0.0422 AC: 203 AN: 4816

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00572 AC: 389 AN: 68010

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00714 Hom.: 3

Bravo AF: 0.0150

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.35
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10503978; hg19: chr8-35218431;