Variant 6-41028445-G-C 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_173561.3(UNC5CL):c.1485C>G(p.His495Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

UNC5CL
NM_173561.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.82

Variant links:

Genes affected

UNC5CL (HGNC:21203): (unc-5 family C-terminal like) Enables peptidase activity. Acts upstream of or within positive regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of JNK cascade. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

UNC5CL links:

Genome browser will be placed here

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=0.019359708).

BP6

Variant 6-41028445-G-C is Benign according to our data. Variant chr6-41028445-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2223216.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5CL	NM_173561.3 linkuse as main transcript	c.1485C>G	p.His495Gln	missense_variant	9/9	ENST00000244565.8	NP_775832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UNC5CL	ENST00000244565.8 linkuse as main transcript	c.1485C>G	p.His495Gln	missense_variant	9/9	1	NM_173561.3	ENSP00000244565	P1
UNC5CL	ENST00000373164.1 linkuse as main transcript	c.1485C>G	p.His495Gln	missense_variant	8/8	1		ENSP00000362258	P1
UNC5CL	ENST00000470102.1 linkuse as main transcript	n.572C>G		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246156

Hom.:

AF XY:

0.0000822

AC XY:

AN XY:

133878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461194

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000660

AC:

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

Jun 24, 2022

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

0.060

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0020

DANN

Benign

0.44

DEOGEN2

Benign

0.00089

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.28

T;.

M_CAP

Benign

0.0017

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.78

N;N

REVEL

Benign

0.011

Sift

Benign

0.42

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.021

MutPred

0.11

Gain of disorder (P = 0.1129);Gain of disorder (P = 0.1129);

MVP

0.12

MPC

0.12

ClinPred

0.092

GERP RS

-8.7

Varity_R

0.029

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over