Variant 4-76325949-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001394954.1(CCDC158):c.3077A>C(p.His1026Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC158
NM_001394954.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

CCDC158 (HGNC:26374): (coiled-coil domain containing 158)

CCDC158 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC158	NM_001394954.1 linkuse as main transcript	c.3077A>C	p.His1026Pro	missense_variant	23/25	ENST00000682701.1	NP_001381883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC158	ENST00000682701.1 linkuse as main transcript	c.3077A>C	p.His1026Pro	missense_variant	23/25		NM_001394954.1	ENSP00000507278	A1
CCDC158	ENST00000504667.2 linkuse as main transcript	n.2943A>C		non_coding_transcript_exon_variant	11/13	1
CCDC158	ENST00000388914.7 linkuse as main transcript	c.3065A>C	p.His1022Pro	missense_variant	22/24	5		ENSP00000373566	P4	Q5M9N0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461170

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726932

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 07, 2022

The c.3065A>C (p.H1022P) alteration is located in exon 22 (coding exon 21) of the CCDC158 gene. This alteration results from a A to C substitution at nucleotide position 3065, causing the histidine (H) at amino acid position 1022 to be replaced by a proline (P). 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

Benign

0.14

BayesDel_addAF

Benign

0.0069

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.70

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.58

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.15

Sift

Benign

0.032

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.82

MutPred

0.19

Gain of glycosylation at S1019 (P = 0.0118);

MVP

0.63

MPC

0.24

ClinPred

0.96

GERP RS

5.0

Varity_R

0.60

gMVP

0.55

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