4-76313223-G-T

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

3
5
11

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)

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
CCDC158NM_001394954.1 linkc.3301C>A p.Gln1101Lys missense_variant 25/25 ENST00000682701.1 NP_001381883.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC158ENST00000682701.1 linkc.3301C>A p.Gln1101Lys missense_variant 25/25 NM_001394954.1 ENSP00000507278.1 A0A804HIY6
CCDC158ENST00000504667.2 linkn.3167C>A non_coding_transcript_exon_variant 13/131
CCDC158ENST00000388914.7 linkc.3289C>A p.Gln1097Lys missense_variant 24/245 ENSP00000373566.2 Q5M9N0-1

Frequencies

GnomAD3 genomes
AF:
0.000447
AC:
68
AN:
152036
Hom.:
0
Cov.:
33
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:
70
AN:
243726
Hom.:
0
AF XY:
0.000318
AC XY:
42
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.:
1
Cov.:
27
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:
68
AN:
152036
Hom.:
0
Cov.:
33
AF XY:
0.000364
AC XY:
27
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.:
0
Bravo
AF:
0.000393
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00111
AC:
9
ExAC
AF:
0.000340
AC:
41

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 providedclinical testingDepartment 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
T
BayesDel_noAF
Benign
-0.24
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0069
T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.98
D
Vest4
0.49
MVP
0.79
MPC
0.20
ClinPred
0.15
T
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.

Other links and lift over

dbSNP: rs200464150; hg19: chr4-77234376; API