Genetic Variant C8orf82:p.Ala171Thr (chr8-144527482-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001001795.2(C8orf82):c.511G>A(p.Ala171Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,256,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

C8orf82
NM_001001795.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.692

Variant links:

Genes affected

C8orf82 (HGNC:33826): (chromosome 8 open reading frame 82)

C8orf82 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14167345).

BP6

Variant 8-144527482-C-T is Benign according to our data. Variant chr8-144527482-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2391115.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf82	NM_001001795.2 link	c.511G>A	p.Ala171Thr	missense_variant	Exon 3 of 3	ENST00000524821.6	NP_001001795.1	Q6P1X6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C8orf82	ENST00000524821.6 link	c.511G>A	p.Ala171Thr	missense_variant	Exon 3 of 3	1	NM_001001795.2	ENSP00000436621.1	Q6P1X6-1
C8orf82	ENST00000313465 link	c.*486G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000316262.5	J3KNI2
C8orf82	ENST00000532827.1 link	c.643G>A	p.Ala215Thr	missense_variant	Exon 3 of 3	2		ENSP00000437092.1	H0YF29
C8orf82	ENST00000534680.5 link	n.511G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000434593.1	Q6P1X6-1

Frequencies

GnomAD3 genomes

AF:

0.0000532

AC:

AN:

150288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000741

AC:

AN:

1106386

Hom.:

Cov.:

AF XY:

0.0000735

AC XY:

AN XY:

530878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000469

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000756

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000794

Gnomad4 OTH exome

AF:

0.0000921

GnomAD4 genome

AF:

0.0000532

AC:

AN:

150396

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

73470

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000445

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.000168

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 13, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

0.11

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.086

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

PROVEAN

Benign

-0.50

REVEL

Benign

0.032

Sift

Benign

0.41

Sift4G

Benign

0.38

Polyphen

0.032

Vest4

0.098

MutPred

0.35

Loss of helix (P = 0.0093);

MVP

0.030

MPC

0.93

ClinPred

0.36

GERP RS

0.47

Varity_R

0.034

gMVP

0.39

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