Variant rs6753459 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042519.2(C2orf88):c.167C>T(p.Thr56Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,724 control chromosomes in the GnomAD database, including 58,824 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 8427 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50397 hom. )

Consequence

C2orf88
NM_001042519.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Variant links:

Genes affected

C2orf88 (HGNC:28191): (chromosome 2 open reading frame 88) Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2orf88 links:

HIBCH (HGNC:4908): (3-hydroxyisobutyryl-CoA hydrolase) This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

HIBCH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3433566E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf88	NM_001042519.2 linkuse as main transcript	c.167C>T	p.Thr56Ile	missense_variant	2/2	ENST00000340623.4	NP_001035984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf88	ENST00000340623.4 linkuse as main transcript	c.167C>T	p.Thr56Ile	missense_variant	2/2	1	NM_001042519.2	ENSP00000345107	P1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47061

AN:

151938

Hom.:

8393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.264

AC:

65682

AN:

249168

Hom.:

9729

AF XY:

0.260

AC XY:

35208

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.477

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.255

AC:

373053

AN:

1461668

Hom.:

50397

Cov.:

AF XY:

0.254

AC XY:

185043

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.481

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.310

AC:

47148

AN:

152056

Hom.:

8427

Cov.:

AF XY:

0.305

AC XY:

22656

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.467

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.266

Hom.:

11472

Bravo

AF:

0.331

TwinsUK

AF:

0.246

AC:

914

ALSPAC

AF:

0.238

AC:

917

ESP6500AA

AF:

0.447

AC:

1769

ESP6500EA

AF:

0.237

AC:

1970

ExAC

AF:

0.270

AC:

32678

Asia WGS

AF:

0.349

AC:

1210

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0080

DANN

Benign

0.33

DEOGEN2

Benign

0.0027

T;T;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.16

.;T;.;.;T

MetaRNN

Benign

0.00023

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P;P;P

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.41

T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T

Polyphen

0.0

B;.;B;B;B

Vest4

0.038

MPC

0.016

ClinPred

0.0032

GERP RS

-3.0

Varity_R

0.044

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over