Variant 8-68331069-C-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_052958.4(C8orf34):c.57C>G(p.Phe19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,445,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

C8orf34
NM_052958.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0530

Variant links:

Genes affected

C8orf34 (HGNC:30905): (chromosome 8 open reading frame 34) This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment. [provided by RefSeq, Mar 2017]

C8orf34 links:

C8orf34-AS1 (HGNC:27840): (C8orf34 antisense RNA 1)

C8orf34-AS1 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=0.06927949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8orf34	NM_052958.4 linkuse as main transcript	c.57C>G	p.Phe19Leu	missense_variant	1/14	ENST00000518698.6
C8orf34-AS1	NR_038877.1 linkuse as main transcript	n.185+238G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8orf34	ENST00000518698.6 linkuse as main transcript	c.57C>G	p.Phe19Leu	missense_variant	1/14	2	NM_052958.4	P2	Q49A92-6
C8orf34-AS1	ENST00000660308.1 linkuse as main transcript	n.205+238G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145484

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000301

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000464

AC:

AN:

86286

Hom.:

AF XY:

0.00

AC XY:

AN XY:

49206

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000754

AC:

AN:

1300198

Hom.:

Cov.:

AF XY:

0.0000764

AC XY:

AN XY:

641344

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:

0.00

Gnomad4 FIN exome

AF:

0.0000311

Gnomad4 NFE exome

AF:

0.0000916

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145484

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71080

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000301

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Oct 26, 2021

The c.57C>G (p.F19L) alteration is located in exon 1 (coding exon 1) of the C8orf34 gene. This alteration results from a C to G substitution at nucleotide position 57, causing the phenylalanine (F) at amino acid position 19 to be replaced by a leucine (L). 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

0.70

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.81

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.46

M_CAP

Benign

0.014

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.43

REVEL

Benign

0.019

Sift

Benign

0.54

Sift4G

Benign

0.37

Vest4

0.020

MutPred

0.10

Gain of MoRF binding (P = 0.1078);

MVP

0.31

MPC

0.19

ClinPred

0.16

GERP RS

1.1

Varity_R

0.037

gMVP

0.086

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