Variant 4-76313223-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394954.1(CCDC158):c.3301C>A(p.Gln1101Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000538 in 1,606,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

CCDC158
NM_001394954.1 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.34

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC158	NM_001394954.1 link	c.3301C>A	p.Gln1101Lys	missense_variant	25/25	ENST00000682701.1	NP_001381883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC158	ENST00000682701.1 link	c.3301C>A	p.Gln1101Lys	missense_variant	25/25		NM_001394954.1	ENSP00000507278.1	A0A804HIY6
CCDC158	ENST00000504667.2 link	n.3167C>A		non_coding_transcript_exon_variant	13/13	1
CCDC158	ENST00000388914.7 link	c.3289C>A	p.Gln1097Lys	missense_variant	24/24	5		ENSP00000373566.2	Q5M9N0-1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000287

AC:

AN:

243726

Hom.:

AF XY:

0.000318

AC XY:

AN XY:

132238

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000212

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:

0.000521

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000547

AC:

796

AN:

1454054

Hom.:

Cov.:

AF XY:

0.000503

AC XY:

364

AN XY:

723454

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000664

Gnomad4 OTH exome

AF:

0.000715

GnomAD4 genome

AF:

0.000447

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000524

Hom.:

Bravo

AF:

0.000393

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00111

AC:

ExAC

AF:

0.000340

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0069

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Benign

0.033

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.49

MVP

0.79

MPC

0.20

ClinPred

0.15

GERP RS

5.8

Varity_R

0.57

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 23

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