Variant chr8-35235807-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_080872.4(UNC5D):c.23C>G(p.Ala8Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

UNC5D
NM_080872.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Variant links:

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]

UNC5D links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05211872).

BP6

Variant 8-35235807-C-G is Benign according to our data. Variant chr8-35235807-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3186641.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5D	NM_080872.4 linkuse as main transcript	c.23C>G	p.Ala8Gly	missense_variant	1/17	ENST00000404895.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5D	ENST00000404895.7 linkuse as main transcript	c.23C>G	p.Ala8Gly	missense_variant	1/17	1	NM_080872.4	P4	Q6UXZ4-1
UNC5D	ENST00000416672.5 linkuse as main transcript	c.23C>G	p.Ala8Gly	missense_variant	1/18	5		A1
UNC5D	ENST00000420357.5 linkuse as main transcript	c.23C>G	p.Ala8Gly	missense_variant	1/15	5
UNC5D	ENST00000287272.6 linkuse as main transcript	c.23C>G	p.Ala8Gly	missense_variant	1/16	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.018

T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.26

T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.052

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.060

N;N;N;N

REVEL

Benign

0.012

Sift

Benign

1.0

T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.0

B;.;.;.

Vest4

0.082

MutPred

0.28

Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);

MVP

0.068

MPC

0.45

ClinPred

0.034

GERP RS

-1.8

Varity_R

0.040

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over