Variant 6-41030484-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173561.3(UNC5CL):c.1238T>C(p.Phe413Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0003 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

UNC5CL
NM_173561.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2295058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5CL	NM_173561.3 linkuse as main transcript	c.1238T>C	p.Phe413Ser	missense_variant	8/9	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.1238T>C	p.Phe413Ser	missense_variant	8/9	1	NM_173561.3	ENSP00000244565	P1
UNC5CL	ENST00000373164.1 linkuse as main transcript	c.1238T>C	p.Phe413Ser	missense_variant	7/8	1		ENSP00000362258	P1
UNC5CL	ENST00000470102.1 linkuse as main transcript	n.325T>C		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000338

AC:

AN:

251390

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000289

AC:

423

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

214

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000407

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000502

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.1238T>C (p.F413S) alteration is located in exon 8 (coding exon 7) of the UNC5CL gene. This alteration results from a T to C substitution at nucleotide position 1238, causing the phenylalanine (F) at amino acid position 413 to be replaced by a serine (S). 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

0.63

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

T;.

M_CAP

Benign

0.0083

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.71

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.73

N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.92

P;P

Vest4

0.77

MVP

0.79

MPC

0.78

ClinPred

0.030

GERP RS

5.0

Varity_R

0.14

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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