3-113978889-A-G

Variant summary

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

The ENST00000295878.8(CCDC191):ā€‹c.2429T>Cā€‹(p.Leu810Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

CCDC191
ENST00000295878.8 missense

Scores

3
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56
Variant links:
Genes affected
CCDC191 (HGNC:29272): (coiled-coil domain containing 191)

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
CCDC191NM_020817.2 linkuse as main transcriptc.2429T>C p.Leu810Pro missense_variant 15/17 ENST00000295878.8 NP_065868.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC191ENST00000295878.8 linkuse as main transcriptc.2429T>C p.Leu810Pro missense_variant 15/171 NM_020817.2 ENSP00000295878 P1Q8NCU4-1
CCDC191ENST00000527855.1 linkuse as main transcriptn.443T>C non_coding_transcript_exon_variant 3/33
CCDC191ENST00000460813.5 linkuse as main transcriptc.*2498T>C 3_prime_UTR_variant, NMD_transcript_variant 15/162 ENSP00000418382

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152198
Hom.:
0
Cov.:
32
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:
0.00115
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000103
AC:
26
AN:
251248
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00136
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461736
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000882
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000988
AC:
12
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsJan 31, 2024The c.2429T>C (p.L810P) alteration is located in exon 15 (coding exon 15) of the CCDC191 gene. This alteration results from a T to C substitution at nucleotide position 2429, causing the leucine (L) at amino acid position 810 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
Pathogenic
0.72
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-0.54
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.95
MVP
0.58
MPC
1.0
ClinPred
0.62
D
GERP RS
5.5
Varity_R
0.95
gMVP
0.67

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.

Other links and lift over

dbSNP: rs199616776; hg19: chr3-113697736; API