Variant 13-45713572-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152719.3(CBY2):c.547C>A(p.Arg183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,736 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

CBY2
NM_152719.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0320

Variant links:

Genes affected

CBY2 (HGNC:30720): (chibby family member 2) Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

CBY2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0147639215).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBY2	NM_152719.3 linkuse as main transcript	c.547C>A	p.Arg183Ser	missense_variant	3/3	ENST00000310521.6	NP_689932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBY2	ENST00000310521.6 linkuse as main transcript	c.547C>A	p.Arg183Ser	missense_variant	3/3	1	NM_152719.3	ENSP00000309189	P3	Q8NA61-1
CBY2	ENST00000378966.3 linkuse as main transcript	c.439C>A	p.Arg147Ser	missense_variant	2/2	1		ENSP00000368249	A2	Q8NA61-2
CBY2	ENST00000610924.1 linkuse as main transcript	c.439C>A	p.Arg147Ser	missense_variant	3/3	5		ENSP00000480148	A2	Q8NA61-2
CBY2	ENST00000533564.1 linkuse as main transcript	c.466C>A	p.Arg156Ser	missense_variant	2/2	2		ENSP00000435230

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

114

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00130

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000764

AC:

192

AN:

251276

Hom.:

AF XY:

0.000780

AC XY:

106

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.00111

AC:

1616

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

751

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.000743

AC:

113

AN:

152008

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000873

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000873

AC:

106

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00136

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 14, 2023

The c.547C>A (p.R183S) alteration is located in exon 3 (coding exon 3) of the SPERT gene. This alteration results from a C to A substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 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

0.82

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.;.;.

Eigen

Benign

0.089

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.82

T;T;T;.

M_CAP

Benign

0.068

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.1

D;D;.;D

REVEL

Benign

0.23

Sift

Uncertain

0.010

D;D;.;D

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

0.97

D;.;D;D

Vest4

0.79

MVP

0.71

MPC

1.2

ClinPred

0.084

GERP RS

3.3

Varity_R

0.23

gMVP

0.70

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